Follicular B2 Cell Activation and Class Switch Recombination Depend on Autocrine C3ar1/C5ar1 Signaling in B2 Cells.

ABSTRACT

The involvement of complement in B2 cell responses has been regarded as occurring strictly via complement components in plasma. In this study, we show that Ab production and class switch recombination (CSR) depend on autocrine C3a and C5a receptor (C3ar1/C5ar1) signaling in B2 cells. CD40 upregulation, IL-6 production, growth in response to BAFF or APRIL, and AID/Bcl-6 expression, as well as follicular CD4+ cell CD21 production, all depended on this signal transduction. OVA immunization of C3ar1-/-C5ar1-/- mice elicited IgM Ab but no other isotypes, whereas decay accelerating factor (Daf1)-/- mice elicited more robust Ab production and CSR than wild-type (WT) mice. Comparable differences occurred in OVA-immunized µMT recipients of WT, C3ar1-/-C5ar1-/- , and Daf1-/- B2 cells and in hen egg lysozyme-immunized µMT recipients of MD4 B2 cells on each genetic background. B2 cells produced factor I and C3 and autophosphorylated CD19. Immunized C3-/-C5-/- recipients of WT MD4 bone marrow efficiently produced Ab. Thus, B2 cell-produced complement participates in B2 cell activation.