{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:04:22Z","timestamp":1791453862358,"version":"4.3.3"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>CD38 is an ectoenzyme receptor found on hematopoietic cells and its expression is used in the flow cytometric analysis of sub-populations of circulating B cells among peripheral blood mononuclear cells (PBMC) to aid in diagnosing patients with different antibody production defects (AbD). Monoclonal antibodies derived from the sea lamprey Variable Lymphocyte Receptor B (VLRB) are emerging as an alternative to conventional mammalian antibodies. We hypothesized that VLRB MM3 (V-CD38) which specifically recognizes CD38 in a manner correlating with its enzymatic activity could identify terminally differentiated B cells in human PBMC. Here we investigate the ability of V-CD38 as a tool to diagnose patients with diverse immune abnormalities including AbD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The expression of CD38 on CD3<jats:sup>-<\/jats:sup>CD19<jats:sup>+<\/jats:sup>CD27<jats:sup>+<\/jats:sup> plasmablasts and CD3<jats:sup>-<\/jats:sup>CD19<jats:sup>+<\/jats:sup>IgM<jats:sup>hi<\/jats:sup>CD27<jats:sup>-<\/jats:sup> transitional B cells in PBMC was analyzed by flow cytometry using V-CD38 and compared with a commercial conventional antibody to CD38 (C-CD38).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A highly significant correlation (p&amp;lt;0.001, r=0.99) between the percentages of plasmablasts recognized by V-CD38 and C-CD38 was observed among 36 healthy controls (HC), 7 patients with AbD and 24 allergic individuals (AI). The use of V-CD38 enabled improved gating of the CD38 expressing cells (CD38+), aiding in the observation that patients with AbD had significantly lower (p=0.002) CD38+ plasmablasts (0.13%\u00b10.13%) than HC (0.52%\u00b10.57%). Only 61.3% of the transitional B cells detected by C-CD38 were also recognized by V-CD38 (r=0.95, p&amp;lt;0.001) among the 67 participants. AI had significantly reduced V-CD38 and C-CD38 transitional cells compared to HC (p=0.026 and p=0.012, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>V-CD38 is a novel reagent that can assess B cells in human PBMC.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1451232","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T09:54:35Z","timestamp":1730973275000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Characterizing CD38 expression in terminally differentiated B cells using variable lymphocyte receptor B tetramers"],"prefix":"10.3389","volume":"15","author":[{"given":"Arundhati G.","family":"Nair","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Leon-Ponte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vy HD","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon","family":"Sussman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6tz R.A.","family":"Ehrhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyal","family":"Grunebaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.2119\/2006\u201300086","article-title":"Structure and enzymatic functions of human CD38","volume":"12","author":"Lee","year":"2006","journal-title":"Mol Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.597959","article-title":"CD38: an immunomodulatory molecule in inflammation and autoimmunity","volume":"11","author":"Piedra-Quintero","year":"2020","journal-title":"Front Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/cells9010228","article-title":"Roles of CD38 in the immune response to infection","volume":"9","author":"Glar\u00eda","year":"2020","journal-title":"Cells"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-022-04917-5","article-title":"Anti-CD38 antibody therapy for patients with relapsed\/refractory multiple myeloma: differential mechanisms of action and recent clinical trial outcomes","volume":"101","author":"Leleu","year":"2022","journal-title":"Ann Hematol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01271","article-title":"EuroFlow-based flowcytometric diagnostic screening and classification of primary immunodeficiencies of the lymphoid system","volume":"10","author":"van Dongen","year":"2019","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.02.004","article-title":"The european society for immunodeficiencies (ESID) registry working definitions for the clinical diagnosis of inborn errors of immunity","volume":"7","author":"Seidel","year":"2019","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B7","doi-asserted-by":"publisher","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":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.20432","article-title":"Flowcytometric phenotyping of common variable immunodeficiency","volume":"74","author":"Warnatz","year":"2008","journal-title":"Cytometry B Clin Cytom"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.576724","article-title":"Immune monitoring of patients with primary immune regulation disorders unravels higher frequencies of follicular T cells with different profiles that associate with alterations in B cell subsets","volume":"11","author":"Caldirola","year":"2020","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2208","DOI":"10.1016\/j.jaci.2018.02.017","article-title":"Age-associated distribution of normal B-cell and plasma cell subsets in peripheral blood","volume":"141","author":"Blanco","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1146\/annurev-immunol-042617-053028","article-title":"Evolution of alternative adaptive immune systems in vertebrates","volume":"36","author":"Boehm","year":"2018","journal-title":"Annu Rev Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1038\/nature08068","article-title":"Dual nature of the adaptive immune system in lampreys","volume":"459","author":"Guo","year":"2009","journal-title":"Nature"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711619105","article-title":"Structure and specificity of lamprey monoclonal antibodies","volume":"105","author":"Herrin","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.659071","article-title":"Detection and neutralization of SARS-coV-2 using non-conventional variable lymphocyte receptor antibodies of the evolutionarily distant sea lamprey","volume":"12","author":"Leung","year":"2021","journal-title":"Front Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.84738","article-title":"Identification of human plasma cells with a lamprey monoclonal antibody","volume":"1","author":"Yu","year":"2016","journal-title":"JCI Insight"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/cells9040950","article-title":"Detection of human CD38 using variable lymphocyte receptor (VLR) tetramers","volume":"9","author":"Khan","year":"2020","journal-title":"Cells"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-000630","article-title":"Flow cytometric evaluation of CD38 expression levels in the newly diagnosed T-cell acute lymphoblastic leukemia and the effect of chemotherapy on its expression in measurable residual disease, refractory disease and relapsed disease: an implication for anti-CD38 immunotherapy","volume":"8","author":"Tembhare","year":"2020","journal-title":"J Immunother Cancer"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1072462","article-title":"Increased expression of the ectoenzyme CD38 in peripheral blood plasmablasts and plasma cells of patients with systemic sclerosis","volume":"13","author":"Agarbati","year":"2022","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa1663","article-title":"Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy","volume":"349","author":"Lo","year":"2015","journal-title":"Science"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/all.13969","article-title":"Impaired memory B-cell development and antibody maturation with a skewing toward IgE in patients with STAT3 hyper-IgE syndrome","volume":"74","author":"van de Veen","year":"2019","journal-title":"Allergy"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2016.04.016","article-title":"Hyper-igE syndromes and the lung","volume":"37","author":"Freeman","year":"2016","journal-title":"Clin Chest Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1016\/j.jaci.2013.01.053","article-title":"Antibody deficiency in patients with ataxia telangiectasia is caused by disturbed B- and T-cell homeostasis and reduced immune repertoire diversity","volume":"131","author":"Driessen","year":"2013","journal-title":"J Allergy Clin Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.06.035","article-title":"De novo truncating variants in SON cause intellectual disability, congenital malformations, and failure to thrive","volume":"99","author":"Tokita","year":"2016","journal-title":"Am J Hum Genet"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-153544","article-title":"Blood-borne human plasma cells in steady state are derived from mucosal immune responses","volume":"113","author":"Mei","year":"2009","journal-title":"Blood"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/all.12490","article-title":"Regulatory functions of B cells in allergic diseases","volume":"69","author":"Braza","year":"2014","journal-title":"Allergy"},{"key":"B26","doi-asserted-by":"publisher","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":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2011.02609.x","article-title":"Age-matched reference values for B-lymphocyte subpopulations and CVID classifications in children","volume":"74","author":"Schatorj\u00e9","year":"2011","journal-title":"Scand J Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-11-4284","article-title":"Identification and characterization of circulating human transitional B cells","volume":"105","author":"Sims","year":"2005","journal-title":"Blood"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aav8402","article-title":"Chronic allergen exposure drives accumulation of long-lived IgE plasma cells in the bone marrow, giving rise to serological memory","volume":"5","author":"Asrat","year":"2020","journal-title":"Sci Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/j.jaci.2009.06.047","article-title":"Induction of long-lived allergen-specific plasma cells by mucosal allergen challenge","volume":"124","author":"Luger","year":"2009","journal-title":"J Allergy Clin Immunol"},{"key":"B31","doi-asserted-by":"publisher","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":"Cytometry A"},{"key":"B32","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1038\/s41423-020-00520-8","article-title":"Beyond monogenetic rare variants: tackling the low rate of genetic diagnoses in predominantly antibody deficiency","volume":"18","author":"Edwards","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1016\/j.jaci.2016.01.018","article-title":"Mutation in IRF2BP2 is responsible for a familial form of common variable immunodeficiency disorder","volume":"138","author":"Keller","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.06.042","article-title":"Plasma cell deficiency in human subjects with heterozygous mutations in Sec61 translocon alpha 1 subunit (SEC61A1)","volume":"141","author":"Schubert","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1016\/j.jaci.2020.03.025","article-title":"APRIL-dependent lifelong plasmacyte maintenance and immunoglobulin production in humans","volume":"146","author":"Yeh","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2022-580","article-title":"MM3 CAR T: A novel tumor targeting and T cell redirection platform for multiple myeloma","volume":"82","author":"McCachren","year":"2022","journal-title":"Cancer Res"},{"key":"B37","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1182\/blood-2007-06-091744","article-title":"The EUROclass trial: defining subgroups in common variable immunodeficiency","volume":"111","author":"Wehr","year":"2008","journal-title":"Blood"},{"key":"B38","doi-asserted-by":"publisher","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":"78","author":"Pi\u0105tosa","year":"2010","journal-title":"Cytometry B Clin Cytom"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1451232\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T09:54:37Z","timestamp":1730973277000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1451232\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,30]]},"references-count":38,"alternative-id":["10.3389\/fimmu.2024.1451232"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1451232","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,30]]},"article-number":"1451232"}}