Novel roles for murine complement receptors type 1 and 2 I. Regulation of B cell survival and proliferation by CR1/2

Innate components of the immune system, such as complement are known to have a modulatory effect on adaptive immune responses. Complement receptors are expressed by both B and T lymphocytes and play part in antigen presentation and cellular activation and adhesion events. On murine B cells type 1 and 2 complement receptors (CR1/2) are expressed and form a co-receptor complex together with CD19 and CD81. We used CR1/2 specific antibodies to assess the role these receptors might play in regulating cell cycling events of B cells. We show that a CR1/2 specific antibody fragment, 7G6 scFv can induce the proliferation of mature B cells. This effect is countermodulated by FcR crosslinkage and enhanced by BCR engagement. The proliferative effect is severely impaired in Cr2-/- animals, strengthening the involvement of CR1/2. Transitional B cells are prone to apoptotic death by selection events, yet they are rescued from apoptosis by CR1/2 crosslinkage. CR1/2 ligation by 7G6 scFv alone can induce nuclear translocation of NF-kappaB, supporting the above observations.We conclude that engagement of complement receptor 2 of B cells promotes the survival of both mature and transitional B cells. This activity supplements the previously described adjuvant effects of complement.