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

LPS stimulates the TLR4/Myeloid differentiation protein-2 (MD-2) complex and promotes a variety ofimmune responses in B cells. TLR4 has two main signaling pathways, MyD88 and Toll/IL-1R (TIR)-domain-containing adaptor-inducing interferon- (TRIF) pathways, but relatively few studies have examinedthese pathways in B cells. In this study, we investigated MyD88- or TRIF-dependent LPS responses inB cells by utilizing their knockout mice. Compared with wild-type (WT) B cells, MyD88−/−B cells weremarkedly impaired in up-regulation of CD86 and proliferation induced by lipid A moiety of LPS. TRIF−/−Bcells were also impaired in these responses compared with WT B cells, but showed better responses thanMyD88−/−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 inthe CSR. Compared with WT and MyD88−/−B cells, TRIF−/−B cells exhibited reduced cell division, fewerIgG1+cells per division, and decreased activation-induced cytidine deaminase (Aicda) mRNA expressionin response to lipid A plus IL-4. Finally, IgG1 production to trinitrophenyl (TNP)-LPS immunization wasimpaired in TRIF−/−mice, while MyD88−/−mice exhibited increased IgG1 production. Thus, MyD88 andTRIF pathways differently regulate TLR4-induced immune responses in B cells