CD28: a novel negative regulator of plasma cell function and survival. (45.16)

Abstract

Abstract CD28 is a cell surface protein that is critical for the activation of naive T cells. Interestingly, CD28 is also expressed on plasma cells. Plasma cells occur in two versions - short lived ones that appear in the secondary lymphoid organs shortly following activation and the long-lived ones that reside in the bone marrow where they produce antibodies for a life time. Here we examined the role of CD28 expression on long-lived plasma cell function and longevity. To generate a host that lacks CD28 expression only on plasma cells, we adoptively transferred CD28-/- or syngeneic wildtype B cells into B cell deficient, μMT mice. We subsequently immunized the recipient hosts and monitored their serum antibody levels, plasma cell frequencies and phenotype for six months. We observed significantly higher antigen-specific IgM and IgG levels in the recipients of CD28-/- B cells in comparison to wildtype counterparts. Consistent with the higher antibody titers, CD28-/- plasma cells produced more immunoglobulin per cell and were present in greater numbers than wildtype plasma cells. Interestingly, CD28-/- plasma cells expressed higher levels of plasma cell survival factors as compared to wildtype plasma cells. Collectively these results suggest that CD28 is a negative regulator of plasma cell function and survival. Insight on the factors that modulate plasma cells can be applied to improve vaccine-induced antibody responses or regulate self-reactive plasma cells in autoimmunity.