{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:56:42Z","timestamp":1792443402684,"version":"4.5.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"32","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,8,11]]},"abstract":"<jats:p>\n                    The homeostasis of circulating B cell subsets in the peripheral blood of healthy adults is well regulated, but in disease it can be severely disturbed. Thus, a subgroup of patients with common variable immunodeficiency (CVID) presents with an extraordinary expansion of an unusual B cell population characterized by the low expression of CD21. CD21\n                    <jats:sup>low<\/jats:sup>\n                    B cells are polyclonal, unmutated IgM\n                    <jats:sup>+<\/jats:sup>\n                    IgD\n                    <jats:sup>+<\/jats:sup>\n                    B cells but carry a highly distinct gene expression profile which differs from conventional na\u00efve B cells. Interestingly, while clearly not representing a memory population, they do share several features with the recently defined memory-like tissue, Fc receptor-like 4 positive B cell population in the tonsils of healthy donors. CD21\n                    <jats:sup>low<\/jats:sup>\n                    B cells show signs of previous activation and proliferation in vivo, while exhibiting defective calcium signaling and poor proliferation in response to B cell receptor stimulation. CD21\n                    <jats:sup>low<\/jats:sup>\n                    B cells express decreased amounts of homeostatic but increased levels of inflammatory chemokine receptors. This might explain their preferential homing to peripheral tissues like the bronchoalveolar space of CVID or the synovium of rheumatoid arthritis patients. Therefore, as a result of the close resemblance to the gene expression profile, phenotype, function and preferential tissue homing of murine B1 B cells, we suggest that CD21\n                    <jats:sup>low<\/jats:sup>\n                    B cells represent a human innate-like B cell population.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0901984106","type":"journal-article","created":{"date-parts":[[2009,7,29]],"date-time":"2009-07-29T22:00:05Z","timestamp":1248904805000},"page":"13451-13456","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":320,"title":["Circulating CD21\n                    <sup>low<\/sup>\n                    B cells in common variable immunodeficiency resemble tissue homing, innate-like B cells"],"prefix":"10.1073","volume":"106","author":[{"given":"Mirzokhid","family":"Rakhmanov","sequence":"first","affiliation":[{"name":"Centre of Chronic Immunodeficiency and"},{"name":"Division of Rheumatology and Clinical Immunology, University Medical Center Freiburg, 79106 Freiburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baerbel","family":"Keller","sequence":"additional","affiliation":[{"name":"Centre of Chronic Immunodeficiency and"},{"name":"Division of Rheumatology and Clinical Immunology, University Medical Center Freiburg, 79106 Freiburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Gutenberger","sequence":"additional","affiliation":[{"name":"Centre of Chronic Immunodeficiency and"},{"name":"Division of Rheumatology and Clinical Immunology, University Medical Center Freiburg, 79106 Freiburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Foerster","sequence":"additional","affiliation":[{"name":"Centre of Chronic Immunodeficiency and"},{"name":"Division of Rheumatology and Clinical Immunology, University Medical Center Freiburg, 79106 Freiburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Hoenig","sequence":"additional","affiliation":[{"name":"Children's Hospital, University Hospital Ulm, 89075 Ulm, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gertjan","family":"Driessen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"van der Burg","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques J.","family":"van Dongen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Wiech","sequence":"additional","affiliation":[{"name":"Institute for Pathology, University Medical Center Freiburg, 79106 Freiburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Visentini","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, University of Rome La Sapienza, 00185 Rome, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Quinti","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, University of Rome La Sapienza, 00185 Rome, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Prasse","sequence":"additional","affiliation":[{"name":"Department of Pneumology, University Medical Center Freiburg, 79106 Freiburg, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Voelxen","sequence":"additional","affiliation":[{"name":"Centre of Chronic Immunodeficiency and"},{"name":"Division of Rheumatology and Clinical Immunology, University Medical Center Freiburg, 79106 Freiburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Salzer","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, University Medical Center Freiburg, 79106 Freiburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigune","family":"Goldacker","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, University Medical Center Freiburg, 79106 Freiburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Fisch","sequence":"additional","affiliation":[{"name":"Institute for Pathology, University Medical Center Freiburg, 79106 Freiburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Eibel","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, University Medical Center Freiburg, 79106 Freiburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine, University of Ulm and Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Hartmut","family":"Peter","sequence":"additional","affiliation":[{"name":"Centre of Chronic Immunodeficiency and"},{"name":"Division of Rheumatology and Clinical Immunology, University Medical Center Freiburg, 79106 Freiburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Warnatz","sequence":"additional","affiliation":[{"name":"Centre of Chronic Immunodeficiency and"},{"name":"Division of Rheumatology and Clinical Immunology, University Medical Center Freiburg, 79106 Freiburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,8,11]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.20432"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.5.1544"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-091744"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025373601374"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1078\/0171-2985-00198"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2006.07.003"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2004.05.010"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.181347898"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20072683"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-03-0750"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050879"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20072682"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-12-4359"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060964"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/0-387-46530-8_14"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81798-5"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80059-8"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2000.01379.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2000.00604.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2006.00371.x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar77"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.5.2749"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2004.0109.x"},{"key":"e_1_3_3_24_2","doi-asserted-by":"crossref","first-page":"4688","DOI":"10.4049\/jimmunol.160.10.4688","article-title":"Kinetics of establishing the memory B cell population as revealed by CD38 expression","volume":"160","author":"Ridderstad A","year":"1998","unstructured":"A Ridderstad, DM Tarlinton, Kinetics of establishing the memory B cell population as revealed by CD38 expression. J Immunol 160, 4688\u20134695 (1998).","journal-title":"J Immunol"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1997.tb00963.x"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2007.09.017"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086907"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1480"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.3.1531"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxg114"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.12.7779"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2133"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/352532a0"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202460200"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1256"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.4.651"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.1.31"},{"key":"e_1_3_3_38_2","first-page":"287","volume-title":"The Antigen T Cell Receptor: Selected Protocols and Applications","author":"Pannetier C","year":"1998","unstructured":"C Pannetier, P Levraud, A Lim, J Even, P Kourilsky The Antigen T Cell Receptor: Selected Protocols and Applications, ed JR Oksenberg (Chapman & Hall, London), pp. 287\u2013325 (1998)."},{"key":"e_1_3_3_39_2","first-page":"230","article-title":"Detection of clonal B cell populations in paraffin-embedded tissues by polymerase chain reaction","volume":"143","author":"Kuppers R","year":"1993","unstructured":"R Kuppers, M Zhao, K Rajewsky, ML Hansmann, Detection of clonal B cell populations in paraffin-embedded tissues by polymerase chain reaction. Am J Pathol 143, 230\u2013239 (1993).","journal-title":"Am J Pathol"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403202"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0901984106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T11:20:56Z","timestamp":1710501656000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0901984106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,8,11]]},"references-count":40,"journal-issue":{"issue":"32","published-print":{"date-parts":[[2009,8,11]]}},"alternative-id":["10.1073\/pnas.0901984106"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0901984106","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1166205.627133","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,8,11]]},"assertion":[{"value":"2009-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-08-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}