Activated B cells express CD28/B7-independent costimulatory activity

Resting and activated B cells display distinct phenotypes and functional properties. Resting B cells are incompetent accessory cells whereas activated B cells are capable of triggering T cell activation. The up-regulation of expression of the B7 family of molecules has been considered to be the primary reason for this functional conversion of activated B cells. We report here that activation of B cells induces a novel costimulatory activity for induction of T cell proliferation, which is independent of the CD28/B7 costimulatory pathway. B cells activated by different stimuli expressed comparable levels of many of the known counter-receptors for costimulation and intercellular adhesion (B7-1, B7-2, HSA, ICAM-1), but differed markedly in their capacity to activate CD4+ T cells from CD28-deficient (-/-) mice. Activation of B cells via CD40, and to a lesser extent with LPS, induced potent B7/CD28-independent costimulatory activity that resulted in marked augmentation of IL-2-mediated proliferative responses of CD4+ T cells from CD28 -/- mice. The B7/CD28-independent costimulatory pathway was capable of triggering the activation of naive CD4+ T cells, as both sorted CD45RBhigh and isolated high density naive CD4+ T cells from CD28 -/- mice responded vigorously to the costimulation provided by CD40L-activated B cells.