Regulation of B cell self-tolerance by BAFF

To avoid the generation of pathogenic autoantibodies, self-reactive lymphocytes are deleted at several distinct checkpoints during B cell maturation. BAFF is required for mature B cell development and survival but causes B cell hyperplasia and autoimmunity when it is overexpressed. Self-reactive B cells have reduced responsiveness to BAFF and therefore die due to the limiting levels of BAFF available in vivo. Elevated BAFF expression subverts B cell self-tolerance by rescuing self-reactive B cells normally deleted relatively late during maturation. Strongly self-reactive B cells are deleted prior to expression of BAFF-R and are therefore resistant to rescue by BAFF.