The complement regulator CD55 modulates TLR9 signaling and supports survival in marginal zone B cells.

Marginal zone (MZ) B cells bridge innate and adaptive immunity by sensing bloodborne antigens and producing rapid antibody and cytokine responses. When unregulated, MZ B cells are associated with autoimmunity. CD55 is a membrane-bound complement regulator that interferes with complement activation and is another important component of innate and adaptive immunity. MZ B cells express low CD55 in both mice and humans, but the role of CD55 in MZ B cell function is unknown. Using germline knockout (KO) mice, we found that similar numbers of MZ B cells were initially established in 3-wk-old CD55-deficient mice compared with wild-type mice. However, MZ B cells failed to accumulate as mice aged and underwent increased apoptosis independent of alternative complement activation. Following ex vivo stimulation of MZ B cells through TLR9 (Toll-like receptor 9), we observed increased interleukin-6 expression in CD55 KO MZ B cells. In addition, CD55 KO mice exhibited reduced total IgG response following in vivo administration of TLR9 agonist. These findings provide new insights into the role of CD55 in MZ B cell survival and B cell function.