Akt activation by CD40 controls plasma cell and memory B cell differentiation but not germinal center formation by autoreactive B cells (P4032)

Abstract A hallmark of adaptive immunity is the formation of germinal centers that generate long-lived plasma cells and memory B cells. These events are undesirable by autoreactive B cells since they would lead the production of pathogenic autoantibodies and memory B cells that would accrue over a lifetime, but is unknown at a molecular level how this is achieved. To address this question we examined the ability of B cells specific for the SLE-specific self-antigen Sm to respond to antigen in vivo in the presence of functional T cells. Sheep red blood cells (SRBC) have an antigen that binds anti-Sm B cells and therefore immunization of anti-Sm mice with SRBCs provides antigen for anti-Sm B cell activation and activation of functional cognate T cells. We find that anti-Sm B cells from germinal centers in response to SRBC immunization, but fail to generate splenic or bone marrow plasma cells. Secondary, immunization shows the absence of memory B cell formation. BCR and CD40 signaling appears normal in anti-Sm B cells with the exception of an Akt signal by CD40. Our data suggest that Akt activation by CD40 signaling controls the formation of plasma cells and memory B cells by autoreactive B cells of the type activated in murine and human SLE. Experiments are underway to test this possibility.