IgM+IgD+CD27+ B cells are markedly reduced in IRAK-4-, MyD88-, and TIRAP- but not UNC-93B-deficient patients

Sandra Weller, Mélanie Bonnet, Héloïse Delagreverie, Laura Israel, Maya Chrabieh, László Maródi, Carlos Rodriguez-Gallego, Ben Zion Garty, Chaim Roifman, Andrew C. Issekutz, Simona Eva Zitnik, Cyrille Hoarau, Yildiz Camcioglu, Júlia Vasconcelos, Carlos Rodrigo, Peter D. Arkwright, Andrea Cerutti, Eric Meffre, Shen Ying Zhang, Alexandre AlcaisAnne Puel, Jean Laurent Casanova, Capucine Picard, Jean Claude Weill, Claude Agnès Reynaud

    Research output: Contribution to journalArticlepeer-review


    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-associated 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-dependent 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. © 2012 by The American Society of Hematology.
    Original languageEnglish
    Pages (from-to)4992-5001
    Number of pages9
    Issue number25
    Publication statusPublished - 13 Dec 2012


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