CD40-mediated activation of the NF-κB2 pathway

CD40 is a critical stimulatory receptor on antigen-presenting cells of the immune system. CD40-mediated activation of B cells is particularly important for normal humoral immune function. Engagement of CD40 by its ligand, CD154, on the surface of activated T cells initiates a variety of signals in B cells including the activation of MAP kinases and NE-kappa B. The transcriptional regulator NE-kappa B is in reality a family of factors that can promote B cell activation, differentiation, and proliferation. Complex and only partially understood biochemical mechanisms allow CD40 to trigger two distinct NE-kappa B activation pathways resulting in the activation of canonical (NF-kappa B1) and non-canonical (NF-kappa B2) NF-kappa B. This brief review provides a summary of mechanisms responsible for activation of the latter, which appears to be particularly important for enhancing the viability of B cells at various stages in their life cycle and may also contribute to the development of B cell malignancies. CD40 is also expressed by various cell types in addition to B cells, including T cells, macrophages, dendritic cells, as well as certain non-hematopoietic cells. Here too, while perhaps less extensively studied than in B cells, the CD40-mediated activation of NF-kappa B2 also appears to have important roles in cellular physiology.