MyD88 is required for viral-induced B cell activation and intestinal IgA production (44.20)

The role of TLR signaling in the induction of specific antibody responses is controversial and defined primarily using model antigens. Our study objective was to determine whether TLR signaling is required to generate pathogen-specific antibody responses. To assess whether TLR signaling is required for a viral-specific intestinal B cell responses, we examined whether B cell responses were aberrant after rotavirus infection of mice lacking expression of specific adapter proteins used in TLR signaling (MyD88, TIRAP, TRIF). Rotavirus infection of MyD88-/- mice did not result in a significant induction of either B cell activation or intestinal rotavirus-specific IgA. In contrast, mice lacking TIRAP and TRIF expression had wild type levels of both B cell activation and intestinal IgA production. B cell activation was normal in mice with a defect in BCR signaling (xid) or mice expressing an OVA-specific BCR, indicating that rotavirus-induced B cell activation does not require a rotavirus-specific BCR. These findings indicate that BCR-independent signaling through MyD88 plays a critical role in pathogen induced B cell activation and the generation of pathogen-specific intestinal IgA. This work was supported by NIH AI10604, AI24998, and by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs.