Differential requirements of MyD88 and TRIF pathways in TLR4-mediated immune responses in murine B cells.

Abstract LPS stimulates the TLR4/Myeloid differentiation protein-2 (MD-2) complex and promotes a variety of immune responses in B cells. TLR4 has two main signaling pathways, MyD88 and Toll/IL-1R (TIR)-domain-containing adaptor-inducing interferon-β (TRIF) pathways, but relatively few studies have examined these pathways in B cells. In this study, we investigated MyD88- or TRIF-dependent LPS responses in B cells by utilizing their knockout mice. Compared with wild-type (WT) B cells, MyD88 −/− B cells were markedly impaired in up-regulation of CD86 and proliferation induced by lipid A moiety of LPS. TRIF −/− B cells were also impaired in these responses compared with WT B cells, but showed better responses than MyD88 −/− B cells. Regarding class switch recombination (CSR) elicited by lipid A plus IL-4, MyD88 −/− B cells showed similar patterns of CSR to WT B cells. However, TRIF −/− B cells showed the impaired in the CSR. Compared with WT and MyD88 −/− B cells, TRIF −/− B cells exhibited reduced cell division, fewer IgG1 + cells per division, and decreased activation-induced cytidine deaminase ( Aicda ) mRNA expression in response to lipid A plus IL-4. Finally, IgG1 production to trinitrophenyl (TNP)-LPS immunization was impaired in TRIF −/− mice, while MyD88 −/− mice exhibited increased IgG1 production. Thus, MyD88 and TRIF pathways differently regulate TLR4-induced immune responses in B cells.