MZ B cells from 14-week-old WT C57BL/6 and CD55 KO mice

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 mice, we found that similar numbers of MZ B cells were initially established in 3-week-old CD55-deficient mice compared to wild-type (WT) 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 Toll-like receptor 9 (TLR9), we observed increased IL-6 expression in CD55 KO MZ B cells. In addition, CD55 KO mice exhibited reduced total IgG response with in vivo administration of TLR9 agonist. These findings provide new insights to the role of CD55 in MZ B cell survival and B cell function. Overall design: Bulk RNA-seq of MZ B cells after negative selection for B cells, then flowsorting for MZ B cells from 14-week-old WT C57BL/6 and CD55 KO mice