NF-kappaB pathways in the immune system: control of the germinal center reaction

The NF-kappaB signaling pathway plays a critical role in regulating innate and adaptive immunity. This is clearly evident as mouse models deficient for numerous NF-kappaB subunits and upstream activators exhibit defects in the immune system ranging from impaired development of lymphocytes to defective adaptive immune responses. In this review, we focus on the role that NF-kappaB plays in the germinal center (GC) reaction. Specifically, we discuss the major NF-kappaB subunits and the IkappaB homolog, Bcl-3. Recent findings reveal that Bcl-6, an unrelated transcriptional repressor, is functionally similar to Bcl-3 as both factors may suppress p53 activity to allow for efficient GC formation to occur. We discuss potential mechanisms of action for Bcl-3 and Bcl-6 in this highly complex, but important process of B-cell affinity maturation.