Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Blood, 2012-12, Vol.120 (25), p.4992-5001

Ort / Verlag

Washington, DC: Elsevier Inc

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.