{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:28:29Z","timestamp":1760149709782,"version":"build-2065373602"},"reference-count":102,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T00:00:00Z","timestamp":1693958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["PID2019-109583RB-I00\/AEI\/10.13039\/501100011033","GLD15\/00303","PI22CIII\/00030","PRE_2018_2_0242","PRE_2021_2_0215","FJGB18\/002","FJGB19\/002","PT20\/00138","CB22\/01\/00041","CB21\/13\/00091"],"award-info":[{"award-number":["PID2019-109583RB-I00\/AEI\/10.13039\/501100011033","GLD15\/00303","PI22CIII\/00030","PRE_2018_2_0242","PRE_2021_2_0215","FJGB18\/002","FJGB19\/002","PT20\/00138","CB22\/01\/00041","CB21\/13\/00091"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Gilead Fellowship Program","award":["PID2019-109583RB-I00\/AEI\/10.13039\/501100011033","GLD15\/00303","PI22CIII\/00030","PRE_2018_2_0242","PRE_2021_2_0215","FJGB18\/002","FJGB19\/002","PT20\/00138","CB22\/01\/00041","CB21\/13\/00091"],"award-info":[{"award-number":["PID2019-109583RB-I00\/AEI\/10.13039\/501100011033","GLD15\/00303","PI22CIII\/00030","PRE_2018_2_0242","PRE_2021_2_0215","FJGB18\/002","FJGB19\/002","PT20\/00138","CB22\/01\/00041","CB21\/13\/00091"]}]},{"name":"Agencia Estatal de Investigaci\u00f3n-ISCIII","award":["PID2019-109583RB-I00\/AEI\/10.13039\/501100011033","GLD15\/00303","PI22CIII\/00030","PRE_2018_2_0242","PRE_2021_2_0215","FJGB18\/002","FJGB19\/002","PT20\/00138","CB22\/01\/00041","CB21\/13\/00091"],"award-info":[{"award-number":["PID2019-109583RB-I00\/AEI\/10.13039\/501100011033","GLD15\/00303","PI22CIII\/00030","PRE_2018_2_0242","PRE_2021_2_0215","FJGB18\/002","FJGB19\/002","PT20\/00138","CB22\/01\/00041","CB21\/13\/00091"]}]},{"name":"Department of Education, Basque Government","award":["PID2019-109583RB-I00\/AEI\/10.13039\/501100011033","GLD15\/00303","PI22CIII\/00030","PRE_2018_2_0242","PRE_2021_2_0215","FJGB18\/002","FJGB19\/002","PT20\/00138","CB22\/01\/00041","CB21\/13\/00091"],"award-info":[{"award-number":["PID2019-109583RB-I00\/AEI\/10.13039\/501100011033","GLD15\/00303","PI22CIII\/00030","PRE_2018_2_0242","PRE_2021_2_0215","FJGB18\/002","FJGB19\/002","PT20\/00138","CB22\/01\/00041","CB21\/13\/00091"]}]},{"name":"Jes\u00fas de Gangoiti Barrera Foundation","award":["PID2019-109583RB-I00\/AEI\/10.13039\/501100011033","GLD15\/00303","PI22CIII\/00030","PRE_2018_2_0242","PRE_2021_2_0215","FJGB18\/002","FJGB19\/002","PT20\/00138","CB22\/01\/00041","CB21\/13\/00091"],"award-info":[{"award-number":["PID2019-109583RB-I00\/AEI\/10.13039\/501100011033","GLD15\/00303","PI22CIII\/00030","PRE_2018_2_0242","PRE_2021_2_0215","FJGB18\/002","FJGB19\/002","PT20\/00138","CB22\/01\/00041","CB21\/13\/00091"]}]},{"name":"Instituto de Salud Carlos III","award":["PID2019-109583RB-I00\/AEI\/10.13039\/501100011033","GLD15\/00303","PI22CIII\/00030","PRE_2018_2_0242","PRE_2021_2_0215","FJGB18\/002","FJGB19\/002","PT20\/00138","CB22\/01\/00041","CB21\/13\/00091"],"award-info":[{"award-number":["PID2019-109583RB-I00\/AEI\/10.13039\/501100011033","GLD15\/00303","PI22CIII\/00030","PRE_2018_2_0242","PRE_2021_2_0215","FJGB18\/002","FJGB19\/002","PT20\/00138","CB22\/01\/00041","CB21\/13\/00091"]}]},{"name":"Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN","award":["PID2019-109583RB-I00\/AEI\/10.13039\/501100011033","GLD15\/00303","PI22CIII\/00030","PRE_2018_2_0242","PRE_2021_2_0215","FJGB18\/002","FJGB19\/002","PT20\/00138","CB22\/01\/00041","CB21\/13\/00091"],"award-info":[{"award-number":["PID2019-109583RB-I00\/AEI\/10.13039\/501100011033","GLD15\/00303","PI22CIII\/00030","PRE_2018_2_0242","PRE_2021_2_0215","FJGB18\/002","FJGB19\/002","PT20\/00138","CB22\/01\/00041","CB21\/13\/00091"]}]},{"name":"CIBER\u2014Consorcio Centro de Investigaci\u00f3n Biom\u00e9dica en Red","award":["PID2019-109583RB-I00\/AEI\/10.13039\/501100011033","GLD15\/00303","PI22CIII\/00030","PRE_2018_2_0242","PRE_2021_2_0215","FJGB18\/002","FJGB19\/002","PT20\/00138","CB22\/01\/00041","CB21\/13\/00091"],"award-info":[{"award-number":["PID2019-109583RB-I00\/AEI\/10.13039\/501100011033","GLD15\/00303","PI22CIII\/00030","PRE_2018_2_0242","PRE_2021_2_0215","FJGB18\/002","FJGB19\/002","PT20\/00138","CB22\/01\/00041","CB21\/13\/00091"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>CD300a is differentially expressed among B cell subsets, although its expression in immunoglobulin (Ig)M+ B cells is not well known. We identified a B cell subset expressing CD300a and high levels of IgM (IgMhiCD300a+). The results showed that IgMhiCD300a+ B cells were CD10\u2212CD27+CD25+IgDloCD21hiCD23\u2212CD38loCD1chi, suggesting that they are circulating marginal zone (MZ) IgM memory B cells. Regarding the immunoglobulin repertoire, IgMhiCD300a+ B cells exhibited a higher mutation rate and usage of the IgH-VDJ genes than the IgM+CD300a\u2212 counterpart. Moreover, the shorter complementarity-determining region 3 (CDR3) amino acid (AA) length from IgMhiCD300a+ B cells together with the predicted antigen experience repertoire indicates that this B cell subset has a memory phenotype. IgM memory B cells are important in T cell-independent responses. Accordingly, we demonstrate that this particular subset secretes higher amounts of IgM after stimulation with pneumococcal polysaccharides or a toll-like receptor 9 (TLR9) agonist than IgM+CD300a\u2212 cells. Finally, the frequency of IgMhiCD300a+ B cells was lower in people living with HIV-1 (PLWH) and it was inversely correlated with the years with HIV infection. Altogether, these data help to identify a memory B cell subset that contributes to T cell-independent responses to pneumococcal infections and may explain the increase in severe pneumococcal infections and the impaired responses to pneumococcal vaccination in PLWH.<\/jats:p>","DOI":"10.3390\/ijms241813754","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T10:07:37Z","timestamp":1693994857000},"page":"13754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Human IgMhiCD300a+ B Cells Are Circulating Marginal Zone Memory B Cells That Respond to Pneumococcal Polysaccharides and Their Frequency Is Decreased in People Living with HIV"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5292-1851","authenticated-orcid":false,"given":"Joana","family":"Vitall\u00e9","sequence":"first","affiliation":[{"name":"Immunopathology Group, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain"},{"name":"Instituto de Biomedicina de Sevilla (IBiS), Virgen del Roc\u00edo University Hospital, CSIC, University of Seville, 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olatz","family":"Zenarruzabeitia","sequence":"additional","affiliation":[{"name":"Immunopathology Group, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7571-1520","authenticated-orcid":false,"given":"Aitana","family":"Merino-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Immunopathology Group, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8099-3916","authenticated-orcid":false,"given":"I\u00f1igo","family":"Terr\u00e9n","sequence":"additional","affiliation":[{"name":"Immunopathology Group, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ane","family":"Orrantia","sequence":"additional","affiliation":[{"name":"Immunopathology Group, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arantza","family":"Pacho de Lucas","sequence":"additional","affiliation":[{"name":"Regulation of the Immune System Group, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain"},{"name":"Immunology Service, Cruces University Hospital, 48903 Barakaldo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 A.","family":"Iribarren","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Donostia University Hospital, Biodonostia Health Research Institute, 20014 Donostia-San Sebasti\u00e1n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2512-6107","authenticated-orcid":false,"given":"Lucio J.","family":"Garc\u00eda-Fraile","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Internal Medicine, La Princesa University Hospital, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luz","family":"Balsalobre","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, UR Salud, Infanta Sof\u00eda University Hospital, 28702 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Amo","sequence":"additional","affiliation":[{"name":"Immunopathology Group, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain"},{"name":"Ikerbasque, Basque Foundation for Science, 48009 Bilbao, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7391-2823","authenticated-orcid":false,"given":"Bel\u00e9n","family":"de Andr\u00e9s","sequence":"additional","affiliation":[{"name":"Immunobiology Department, Carlos III Health Institute, 28220 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3105-981X","authenticated-orcid":false,"given":"Francisco","family":"Borrego","sequence":"additional","affiliation":[{"name":"Immunopathology Group, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain"},{"name":"Ikerbasque, Basque Foundation for Science, 48009 Bilbao, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.1002\/(SICI)1521-4141(199910)29:10<3148::AID-IMMU3148>3.0.CO;2-L","article-title":"Molecular and Functional Characterization of IRp60, a Member of the Immunoglobulin Superfamily That Functions as an Inhibitory Receptor in Human NK Cells","volume":"29","author":"Cantoni","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"DeBell, K.E., Simhadri, V.R., Mariano, J.L., and Borrego, F. (2012). Functional Requirements for Inhibitory Signal Transmission by the Immunomodulatory Receptor CD300a. BMC Immunol., 13.","DOI":"10.1186\/1471-2172-13-23"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1182\/blood-2012-09-435057","article-title":"The CD300 Molecules: An Emerging Family of Regulators of the Immune System","volume":"121","author":"Borrego","year":"2013","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5053","DOI":"10.4049\/jimmunol.1500304","article-title":"The Biology and Disease Relevance of CD300a, an Inhibitory Receptor for Phosphatidylserine and Phosphatidylethanolamine","volume":"194","author":"Zenarruzabeitia","year":"2015","journal-title":"J. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1002\/eji.201847951","article-title":"CD300 Receptor Family in Viral Infections","volume":"49","author":"Orrantia","year":"2019","journal-title":"Eur. J. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"106826","DOI":"10.1016\/j.actatropica.2023.106826","article-title":"Leishmania Donovani Induces CD300a Expression to Dampen Effector Properties of CD11c+ Dendritic and Antigen Activated CD8+ T Cells","volume":"239","author":"Anand","year":"2023","journal-title":"Acta Trop."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"793611","DOI":"10.3389\/fimmu.2021.793611","article-title":"CD300a Receptor Blocking Enhances Early Clearance of Leishmania Donovani from Its Mammalian Host Through Modulation of Effector Functions of Phagocytic and Antigen Experienced T Cells","volume":"12","author":"Singh","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1128\/JVI.01849-15","article-title":"The Phosphatidylserine and Phosphatidylethanolamine Receptor CD300a Binds Dengue Virus and Enhances Infection","volume":"90","author":"Carnec","year":"2015","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1128\/JVI.02902-15","article-title":"Pseudorabies Virus US3 Protein Kinase Protects Infected Cells from NK Cell-Mediated Lysis via Increased Binding of the Inhibitory NK Cell Receptor CD300a","volume":"90","author":"Grauwet","year":"2016","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1002\/eji.202049006","article-title":"The Inhibitory Receptor CD300a Is Essential for Neutrophil-Mediated Clearance of Urinary Tract Infection in Mice","volume":"51","author":"Isaacson","year":"2021","journal-title":"Eur. J. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"836","DOI":"10.3389\/fimmu.2017.00836","article-title":"Monocytes Phenotype and Cytokine Production in Human Immunodeficiency Virus-1 Infected Patients Receiving a Modified Vaccinia Ankara-Based HIV-1 Vaccine: Relationship to CD300 Molecules Expression","volume":"8","author":"Zenarruzabeitia","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.3389\/fimmu.2018.01709","article-title":"Altered Expression of CD300a Inhibitory Receptor on CD4+ T Cells from Human Immunodeficiency Virus-1-Infected Patients: Association with Disease Progression Markers","volume":"9","author":"Orrantia","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1038\/s41423-019-0275-4","article-title":"CD300a Inhibits CD16-Mediated NK Cell Effector Functions in HIV-1-Infected Patients","volume":"16","author":"Orrantia","year":"2019","journal-title":"Cell. Mol. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1097\/QAD.0000000000002544","article-title":"CD300a Identifies a CD4+ memory T Cell Subset with a Higher Susceptibility to HIV-1 Infection","volume":"34","author":"Orrantia","year":"2020","journal-title":"Aids"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6070","DOI":"10.1038\/s41598-020-63025-4","article-title":"Polyfunctional HIV-1 Specific Response by CD8+ T Lymphocytes Expressing High Levels of CD300a","volume":"10","author":"Orrantia","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1084\/jem.20120096","article-title":"Apoptotic Cells Suppress Mast Cell Inflammatory Responses via the CD300a Immunoreceptor","volume":"209","author":"Shoji","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1093\/intimm\/dxw047","article-title":"Immunoreceptor CD300a on Mast Cells and Dendritic Cells Regulates Neutrophil Recruitment in a Murine Model of Sepsis","volume":"28","author":"Udayanga","year":"2016","journal-title":"Int. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2877","DOI":"10.4049\/jimmunol.0903347","article-title":"Expression and Function of CD300 in NK Cells","volume":"185","author":"Lankry","year":"2010","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e61999","DOI":"10.7554\/eLife.61999","article-title":"Tumor-Derived Extracellular Vesicles Regulate Tumor-Infiltrating Regulatory T Cells via the Inhibitory Immunoreceptor CD300a","volume":"10","author":"Nakazawa","year":"2021","journal-title":"eLife"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Narayanan, S., Silva, R., Peruzzi, G., Alvarez, Y., Simhadri, V.R., Debell, K., Coligan, J.E., and Borrego, F. (2010). Human Th1 Cells That Express CD300a Are Polyfunctional and After Stimulation Up-Regulate the T-Box Transcription Factor Eomesodermin. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010636"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1177\/1753425913507095","article-title":"Identification of CD300a as a New Hypoxia-Inducible Gene and a Regulator of CCL20 and VEGF Production by Human Monocytes and Macrophages","volume":"20","author":"Raggi","year":"2014","journal-title":"Innate Immun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1002\/JLB.3A1018-389R","article-title":"The Immunoreceptor CD300a Controls the Intensity of Inflammation and Dysfunction in a Model of Ag-Induced Arthritis in Mice","volume":"106","author":"Valiate","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"32693","DOI":"10.1038\/srep32693","article-title":"The Expression and Function of Human CD300 Receptors on Blood Circulating Mononuclear Cells Are Distinct in Neonates and Adults","volume":"6","author":"Zenarruzabeitia","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nature14231","article-title":"Signalling Thresholds and Negative B-Cell Selection in Acute Lymphoblastic Leukaemia","volume":"521","author":"Chen","year":"2015","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5870","DOI":"10.1182\/blood-2010-09-310318","article-title":"CD300a Is Expressed on Human B Cells, Modulates BCR-Mediated Signaling, and Its Expression Is down-Regulated in HIV Infection","volume":"117","author":"Silva","year":"2011","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"594813","DOI":"10.3389\/fimmu.2020.594813","article-title":"Direct Infection of B Cells by Dengue Virus Modulates B Cell Responses in a Cambodian Pediatric Cohort","volume":"11","author":"Upasani","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/cyto.a.24507","article-title":"Comprehensive Phenotyping of Human Peripheral Blood B Lymphocytes in Healthy Conditions","volume":"101","author":"Carsetti","year":"2022","journal-title":"Cytom. Part A"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8212","DOI":"10.4049\/jimmunol.178.12.8212","article-title":"Loss of Discrete Memory B Cell Subsets Is Associated with Impaired Immunization Responses in HIV-1 Infection and May Be a Risk Factor for Invasive Pneumococcal Disease","volume":"178","author":"Hart","year":"2007","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/eji.201646642","article-title":"Human B-Cell Memory Is Shaped by Age- and Tissue-Specific T-Independent and GC-Dependent Events","volume":"47","author":"Aranburu","year":"2017","journal-title":"Eur. J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.3389\/fimmu.2019.01787","article-title":"Remembrance of Things Past: Long-Term B Cell Memory After Infection and Vaccination","volume":"10","author":"Palm","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.imlet.2013.04.007","article-title":"Why Do We Need IgM Memory B Cells?","volume":"152","author":"Capolunghi","year":"2013","journal-title":"Immunol. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3647","DOI":"10.1182\/blood-2004-01-0346","article-title":"Human Blood IgM \u201cMemory\u201d B Cells Are Circulating Splenic Marginal Zone B Cells Harboring a Prediversified Immunoglobulin Repertoire","volume":"104","author":"Weller","year":"2004","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"889876","DOI":"10.3389\/fimmu.2022.889876","article-title":"Role of IgM Memory B Cells and Spleen Function in COVID-19","volume":"13","author":"Rossi","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13","DOI":"10.4049\/jimmunol.179.1.13","article-title":"Human IgM+CD27+ B Cells: Memory B Cells or \u201cMemory\u201d B Cells?","volume":"179","author":"Tangye","year":"2007","journal-title":"J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/1521-4141(200101)31:1<243::AID-IMMU243>3.0.CO;2-0","article-title":"IgG Subclass Switch Capacity Is Low in Switched and in IgM-Only, but High in IgD+IgM+, Post-Germinal Center (CD27+) Human B Cells","volume":"31","author":"Bovia","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/s41577-019-0244-2","article-title":"B Cell Memory: Building Two Walls of Protection against Pathogens","volume":"20","author":"Akkaya","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coi.2019.09.003","article-title":"IgM Memory B Cells: Specific Effectors of Innate-like and Adaptive Responses","volume":"63","author":"Weill","year":"2020","journal-title":"Curr. Opin. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"736","DOI":"10.3389\/fimmu.2020.00736","article-title":"Differential Expression of IgM and IgD Discriminates Two Subpopulations of Human Circulating IgM+IgD+CD27+ B Cells That Differ Phenotypically, Functionally, and Genetically","volume":"11","author":"Bautista","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3389\/fimmu.2011.00081","article-title":"The Relationship between CD27 Negative and Positive B Cell Populations in Human Peripheral Blood","volume":"2","author":"Wu","year":"2011","journal-title":"Front. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1146\/annurev.immunol.021908.132607","article-title":"Human Marginal Zone B Cells","volume":"27","author":"Weill","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1084\/jem.20091087","article-title":"Molecular Footprints of a Germinal Center Derivation of Human IgM+(IgD+)CD27+ B Cells and the Dynamics of Memory B Cell Generation","volume":"206","author":"Seifert","year":"2009","journal-title":"J. Exp. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1038\/leu.2016.226","article-title":"Human Memory B Cells","volume":"30","author":"Seifert","year":"2016","journal-title":"Leukemia"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1084\/jem.188.9.1679","article-title":"Human Immunoglobulin (Ig)M+IgD+ Peripheral Blood B Cells Expressing the CD27 Cell Surface Antigen Carry Somatically Mutated Variable Region Genes: CD27 as a General Marker for Somatically Mutated (Memory) B Cells","volume":"188","author":"Klein","year":"1998","journal-title":"J. Exp. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"E5281","DOI":"10.1073\/pnas.1511270112","article-title":"Complexity of the Human Memory B-Cell Compartment Is Determined by the Versatility of Clonal Diversification in Germinal Centers","volume":"112","author":"Budeus","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.3389\/fimmu.2019.02458","article-title":"Challenges and Opportunities for Consistent Classification of Human B Cell and Plasma Cell Populations","volume":"10","author":"Sanz","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1084\/jem.20022020","article-title":"Human Immunoglobulin M Memory B Cells Controlling Streptococcus pneumoniae Infections Are Generated in the Spleen","volume":"197","author":"Kruetzmann","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.jaci.2004.10.048","article-title":"The Loss of IgM Memory B Cells Correlates with Clinical Disease in Common Variable Immunodeficiency","volume":"115","author":"Carsetti","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"25629","DOI":"10.1038\/srep25629","article-title":"CD23 Can Negatively Regulate B-Cell Receptor Signaling","volume":"6","author":"Liu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_49","first-page":"29","article-title":"Expression of CD27 and CD23 on Peripheral Blood B Lymphocytes in Humans of Different Ages","volume":"7","author":"Veneri","year":"2009","journal-title":"Blood Transfus."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e20220201","DOI":"10.1084\/jem.20220201","article-title":"Human CD38 Regulates B Cell Antigen Receptor Dynamic Organization in Normal and Malignant B Cells","volume":"219","author":"Camponeschi","year":"2022","journal-title":"J. Exp. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"32","DOI":"10.3389\/fimmu.2020.00032","article-title":"CD11c+ B Cells Are Mainly Memory Cells, Precursors of Antibody Secreting Cells in Healthy Donors","volume":"11","author":"Golinski","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/nri3383","article-title":"Marginal Zone B Cells: Virtues of Innate-like Antibody-Producing Lymphocytes","volume":"13","author":"Cerutti","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"521","DOI":"10.4049\/jimmunol.1102814","article-title":"Recruitment of Memory B Cells to Lymph Nodes Remote from the Site of Immunization Requires an Inflammatory Stimulus","volume":"189","author":"Shenoy","year":"2012","journal-title":"J. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/j.1749-6632.2003.tb06059.x","article-title":"Long-Lived Plasma Cells in Immunity and Inflammation","volume":"987","author":"Hauser","year":"2003","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.4049\/jimmunol.169.3.1277","article-title":"Chemotactic Responsiveness Toward Ligands for CXCR3 and CXCR4 Is Regulated on Plasma Blasts during the Time Course of a Memory Immune Response","volume":"169","author":"Hauser","year":"2002","journal-title":"J. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3965","DOI":"10.1182\/blood-2004-08-2992","article-title":"Regulation of CXCR3 and CXCR4 Expression during Terminal Differentiation of Memory B Cells into Plasma Cells","volume":"105","author":"Muehlinghaus","year":"2005","journal-title":"Blood"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1016\/j.immuni.2017.11.022","article-title":"CCR6 Defines Memory B Cell Precursors in Mouse and Human Germinal Centers, Revealing Light-Zone Location and Predominant Low Antigen Affinity","volume":"47","author":"Suan","year":"2017","journal-title":"Immunity"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"294","DOI":"10.2119\/molmed.2013.00069","article-title":"Expression of Immunoglobulin Receptors with Distinctive Features Indicating Antigen Selection by Marginal Zone B Cells from Human Spleen","volume":"19","author":"Colombo","year":"2013","journal-title":"Mol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"462","DOI":"10.3389\/fimmu.2018.00462","article-title":"Analyzing Immunoglobulin Repertoires","volume":"9","author":"Chaudhary","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/imr.12754","article-title":"The Continuing Story of T-Cell Independent Antibodies","volume":"288","author":"Allman","year":"2019","journal-title":"Immunol. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"11230","DOI":"10.1073\/pnas.0809917106","article-title":"Enhanced Humoral Immune Responses against T-Independent Antigens in Fc\u03b1\/\u039cR-Deficient Mice","volume":"106","author":"Honda","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1084\/jem.20120127","article-title":"Distinct Cellular Pathways Select Germline-Encoded and Somatically Mutated Antibodies into Immunological Memory","volume":"209","author":"Kaji","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1084\/jem.20052036","article-title":"T-Independent Type II Immune Responses Generate Memory B Cells","volume":"203","author":"Obukhanych","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1002\/eji.201343716","article-title":"Generation of Memory B Cells inside and Outside Germinal Centers","volume":"44","author":"Takemori","year":"2014","journal-title":"Eur. J. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1084\/jem.20111696","article-title":"A Germinal Center\u2013Independent Pathway Generates Unswitched Memory B Cells Early in the Primary Response","volume":"209","author":"Taylor","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1002\/eji.1830180918","article-title":"B Cell Memory to Thymus-Independent Antigens Type 1 and Type 2: The Role of Lipopolysaccharide in B Memory Induction","volume":"18","author":"Zhang","year":"1988","journal-title":"Eur. J. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"872","DOI":"10.3389\/fimmu.2017.00872","article-title":"Defining Natural Antibodies","volume":"8","author":"Holodick","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.3389\/fimmu.2020.02139","article-title":"Current Understanding of Natural Antibodies and Exploring the Possibilities of Modulation Using Veterinary Models. A Review","volume":"11","author":"Reyneveld","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.3389\/fimmu.2018.02242","article-title":"Marginal-Zone B-Cells Are Main Producers of IgM in Humans, and Are Reduced in Patients with Autoimmune Vasculitis","volume":"9","author":"Appelgren","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"7293","DOI":"10.4049\/jimmunol.1002722","article-title":"TLR Ligation Triggers Somatic Hypermutation in Transitional B Cells Inducing the Generation of IgM Memory B Cells","volume":"185","author":"Aranburu","year":"2010","journal-title":"J. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Doyon-Lalibert\u00e9, K., Aranguren, M., Poudrier, J., and Roger, M. (2022). Marginal Zone B-Cell Populations and Their Regulatory Potential in the Context of HIV and Other Chronic Inflammatory Conditions. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23063372"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/j.1365-3083.2007.01946.x","article-title":"The Human Immunomodulatory CD25+ B Cell Population Belongs to the Memory B Cell Pool","volume":"66","author":"Amu","year":"2007","journal-title":"Scand. J. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1126\/science.1067308","article-title":"Requirement of the Activation-Induced Deaminase (AID) Gene for Immunoglobulin Gene Conversion","volume":"295","author":"Arakawa","year":"2002","journal-title":"Science"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1093\/intimm\/14.2.157","article-title":"CD23 Defines Two Distinct Subsets of Immature B Cells Which Differ in Their Responses to T Cell Help Signals","volume":"14","author":"Chung","year":"2002","journal-title":"Int. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"102627","DOI":"10.1016\/j.jaut.2021.102627","article-title":"Marginal Zone B Cells: From Housekeeping Function to Autoimmunity?","volume":"119","author":"Palm","year":"2021","journal-title":"J. Autoimmun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1111\/all.14288","article-title":"CD23 Expression on Switched Memory B Cells Bridges T-B Cell Interaction in Allergic Rhinitis","volume":"75","author":"Yao","year":"2020","journal-title":"Allergy"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Cameron, P.U., Jones, P., Gorniak, M., Dunster, K., Paul, E., Lewin, S., Woolley, I., and Spelman, D. (2011). Splenectomy Associated Changes in IgM Memory B Cells in an Adult Spleen Registry Cohort. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023164"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1365-2249.2010.04206.x","article-title":"Reference Values for B Cell Subpopulations from Infancy to Adulthood","volume":"162","author":"Morbach","year":"2010","journal-title":"Clin. Exp. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1002\/cyto.b.20536","article-title":"B Cell Subsets in Healthy Children: Reference Values for Evaluation of B Cell Maturation Process in Peripheral Blood","volume":"78B","author":"Pac","year":"2010","journal-title":"Cytom. Part B Clin. Cytom."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.clim.2009.05.020","article-title":"Refined Characterization and Reference Values of the Pediatric T- and B-Cell Compartments","volume":"133","author":"Nibbelke","year":"2009","journal-title":"Clin. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1084\/jem.20041185","article-title":"The Role of CXCR4 in Maintaining Peripheral B Cell Compartments and Humoral Immunity","volume":"200","author":"Nie","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"34998","DOI":"10.1074\/jbc.M002089200","article-title":"Ligation of HLA-DR Molecules on B Cells Induces Enhanced Expression of IgM Heavy Chain Genes in Association with Syk Activation","volume":"275","author":"Tabata","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"890","DOI":"10.4049\/jimmunol.182.2.890","article-title":"Resting Human Memory B Cells Are Intrinsically Programmed for Enhanced Survival and Responsiveness to Diverse Stimuli Compared to Naive B Cells","volume":"182","author":"Good","year":"2009","journal-title":"J. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1016\/j.celrep.2019.10.087","article-title":"Transcription Factor T-Bet in B Cells Modulates Germinal Center Polarization and Antibody Affinity Maturation in Response to Malaria","volume":"29","author":"Ly","year":"2019","journal-title":"Cell Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1615\/CritRevImmunol.2018024985","article-title":"Heterogeneity of Memory Marginal Zone B Cells","volume":"38","author":"Hendricks","year":"2018","journal-title":"Crit. Rev. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1182\/blood-2010-03-275859","article-title":"High-Throughput Immunoglobulin Repertoire Analysis Distinguishes between Human IgM Memory and Switched Memory B-Cell Populations","volume":"116","author":"Wu","year":"2010","journal-title":"Blood"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1007\/s00018-012-0971-z","article-title":"IgM Memory B Cells: A Mouse\/Human Paradox","volume":"69","author":"Reynaud","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"800","DOI":"10.4049\/jimmunol.180.2.800","article-title":"CpG Drives Human Transitional B Cells to Terminal Differentiation and Production of Natural Antibodies","volume":"180","author":"Capolunghi","year":"2008","journal-title":"J. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Hendricks, J., Visser, A., Dammers, P.M., Burgerhof, J.G.M., Bos, N.A., and Kroese, F.G.M. (2019). The Formation of Mutated IgM Memory B Cells in Rat Splenic Marginal Zones Is an Antigen Dependent Process. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0220933"},{"key":"ref_90","unstructured":"Gurbanov, R. (2021). Polysaccharides, Scrivener Publishing LLC."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1093\/clinids\/14.1.251","article-title":"Mechanisms of Host Defense against Infection with Streptococcus pneumoniae","volume":"14","author":"Bruyn","year":"1992","journal-title":"Clin. Infect. Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"690534","DOI":"10.3389\/fimmu.2021.690534","article-title":"Evolution of Human Memory B Cells from Childhood to Old Age","volume":"12","author":"Ciocca","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/j.1749-6632.2011.06329.x","article-title":"Mechanisms Underlying in Vivo Polysaccharide-Specific Immunoglobulin Responses to Intact Extracellular Bacteria","volume":"1253","author":"Snapper","year":"2012","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1128\/iai.59.5.1839-1845.1991","article-title":"Pneumococcal Polysaccharides Complexed with C3d Bind to Human B Lymphocytes via Complement Receptor Type 2","volume":"59","author":"Griffioen","year":"1991","journal-title":"Infect. Immun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S1074-7613(00)80418-5","article-title":"The CD19-CD21 Complex Regulates Signal Transduction Thresholds Governing Humoral Immunity and Autoimmunity","volume":"6","author":"Tedder","year":"1997","journal-title":"Immunity"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3736","DOI":"10.4049\/jimmunol.1401413","article-title":"TLR-Mediated Inflammatory Responses to Streptococcus pneumoniae Are Highly Dependent on Surface Expression of Bacterial Lipoproteins","volume":"193","author":"Tomlinson","year":"2014","journal-title":"J. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1089\/088922204773004941","article-title":"Selective CD27 (Memory) B Cell Reduction and Characteristic B Cell Alteration in Drug-Naive and HAART-Treated HIV Type 1-Infected Patients","volume":"20","author":"Chong","year":"2004","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.3389\/fimmu.2017.01056","article-title":"Selective IgM Deficiency\u2014An Underestimated Primary Immunodeficiency","volume":"8","author":"Gupta","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1011607","DOI":"10.3389\/fimmu.2022.1011607","article-title":"Age-Dependent Nasal Immune Responses in Non-Hospitalized Bronchiolitis Children","volume":"13","author":"Cortegano","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Christley, S., Levin, M.K., Toby, I.T., Fonner, J.M., Monson, N.L., Rounds, W.H., Rubelt, F., Scarborough, W., Scheuermann, R.H., and Cowell, L.G. (2017). VDJPipe: A Pipelined Tool for Pre-Processing Immune Repertoire Sequencing Data. BMC Bioinform., 18.","DOI":"10.1186\/s12859-017-1853-z"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"D413","DOI":"10.1093\/nar\/gku1056","article-title":"IMGT R, the International ImMunoGeneTics Information System R 25 Years On","volume":"43","author":"Lefranc","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"4156","DOI":"10.4049\/jimmunol.1601921","article-title":"Antigen Receptor Galaxy: A User-Friendly, Web-Based Tool for Analysis and Visualization of T and B Cell Receptor Repertoire Data","volume":"198","author":"IJspeert","year":"2017","journal-title":"J. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/18\/13754\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:46:10Z","timestamp":1760129170000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/18\/13754"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,6]]},"references-count":102,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["ijms241813754"],"URL":"https:\/\/doi.org\/10.3390\/ijms241813754","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2023,9,6]]}}}