Regulation of B lymphocyte responses to foreign and self-antigens by the CD19/CD21 complex

The membrane protein complex CD19/CD21 couples the innate immune recognitio n of microbial antigens by the complement system to the activation of B cel ls. CD21 binds the C3d fragment of activated C3 that becomes covalently att ached to targets of complement activation, and CD19 co-stimulates signaling through the antigen receptor, membrane immunoglobulin. CD21 is also expres sed by follicular dendritic cells and mediates the long-term retention of a ntigen that is required for the maintenance of memory B cells. Understandin g of the biology of this receptor complex has been enriched by analyses of genetically modified mice; these analyses have uncovered roles not only in positive responses to foreign antigens, but also in the development of tole rance to self-antigens. Studies of signal transduction have begun to determ ine the basis for the coreceptor activities of CD 19. The integration of in nate and adaptive immune recognition at this molecular site on the B cell g uides the appropriate selection of antigen by adaptive immunity and emphasi zes the importance of this coreceptor complex.