{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T02:28:17Z","timestamp":1768098497141,"version":"3.49.0"},"reference-count":51,"publisher":"American Society of Hematology","issue":"25","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,12,13]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We studied the distribution of peripheral B-cell subsets in patients deficient for key factors of the TLR-signaling pathways (MyD88, TIRAP\/MAL, IL-1 receptor\u2013associated kinase 4 [IRAK-4], TLR3, UNC-93B, TRIF). All TLRs, except TLR3, which signals through the TRIF adaptor, require MyD88 and IRAK-4 to mediate their function. TLR4 and the TLR2 heterodimers (with TLR1, TLR6, and possibly TLR10) require in addition the adaptor TIRAP, whereas UNC-93B is needed for the proper localization of intracellular TLR3, TLR7, TLR8, and TLR9. We found that IgM+IgD+CD27+ but not switched B cells were strongly reduced in MyD88-, IRAK-4-, and TIRAP-deficient patients. This defect did not appear to be compensated with age. However, somatic hypermutation of Ig genes and heavy-chain CDR3 size distribution of IgM+IgD+CD27+ B cells were not affected in these patients. In contrast, the numbers of IgM+IgD+CD27+ B cells were normal in the absence of TLR3, TRIF, and UNC-93B, suggesting that UNC-93B\u2013dependent TLRs, and notably TLR9, are dispensable for the presence of this subset in peripheral blood. Interestingly, TLR10 was found to be expressed at greater levels in IgM+IgD+CD27+ compared with switched B cells in healthy patients. Hence, we propose a role for TIRAP-dependent TLRs, possibly TLR10 in particular, in the development and\/or maintenance of IgM+IgD+CD27+ B cells in humans.<\/jats:p>","DOI":"10.1182\/blood-2012-07-440776","type":"journal-article","created":{"date-parts":[[2012,9,23]],"date-time":"2012-09-23T00:16:18Z","timestamp":1348359378000},"page":"4992-5001","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":89,"title":["IgM+IgD+CD27+ B cells are markedly reduced in IRAK-4\u2013, MyD88-, and TIRAP- but not UNC-93B\u2013deficient patients"],"prefix":"10.1182","volume":"120","author":[{"given":"Sandra","family":"Weller","sequence":"first","affiliation":[{"name":"Inserm U783, D\u00e9veloppement du Syst\u00e8me Immunitaire, Facult\u00e9 de M\u00e9decine-Site Necker-Enfants Malades, Universit\u00e9 Paris Descartes, Paris, France;"}]},{"given":"M\u00e9lanie","family":"Bonnet","sequence":"additional","affiliation":[{"name":"Inserm U783, D\u00e9veloppement du Syst\u00e8me Immunitaire, Facult\u00e9 de M\u00e9decine-Site Necker-Enfants Malades, Universit\u00e9 Paris Descartes, Paris, France;"}]},{"given":"H\u00e9lo\u00efse","family":"Delagreverie","sequence":"additional","affiliation":[{"name":"Inserm U783, D\u00e9veloppement du Syst\u00e8me Immunitaire, Facult\u00e9 de M\u00e9decine-Site Necker-Enfants Malades, Universit\u00e9 Paris Descartes, Paris, France;"}]},{"given":"Laura","family":"Israel","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm U980, Universit\u00e9 Paris Descartes, Facult\u00e9 de M\u00e9decine-Site Necker-Enfants Malades, Universit\u00e9 Paris Descartes, Paris, France;"}]},{"given":"Maya","family":"Chrabieh","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm U980, Universit\u00e9 Paris Descartes, Facult\u00e9 de M\u00e9decine-Site Necker-Enfants Malades, Universit\u00e9 Paris Descartes, Paris, France;"}]},{"given":"L\u00e1szl\u00f3","family":"Mar\u00f3di","sequence":"additional","affiliation":[{"name":"Department of Infectious and Pediatric Immunology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary;"}]},{"given":"Carlos","family":"Rodriguez-Gallego","sequence":"additional","affiliation":[{"name":"Department of Immunology, Dr Negrin University Hospital of Gran Canaria, Las Palmas de Gran Canaria, Spain;"}]},{"given":"Ben-Zion","family":"Garty","sequence":"additional","affiliation":[{"name":"Schneider Children's Medical Center, Petah Tiqva, Israel;"}]},{"given":"Chaim","family":"Roifman","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON;"}]},{"given":"Andrew C.","family":"Issekutz","sequence":"additional","affiliation":[{"name":"Dalhousie University, Halifax, NS;"}]},{"given":"Simona 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