NF-κB has a critical role in germinal center (GC) lymphomagenesis. In The Journal of Experimental Medicine, Klein and colleagues use mice with conditional deletion of genes encoding the canonical NF-κB subunits c-Rel and RelA in activated B cells to show that these two subunits have distinct functions at different developmental stages during the GC B cell reaction. RelA is not required for GC formation or affinity maturation but is necessary for the differentiation of GC B cells into plasmablasts. RelA-deficient B cells do not upregulate the transcription factor Blimp-1, which is required for the generation of plasma cells. In contrast, c-Rel is dispensable for plasma cell differentiation but is required for the maintenance of GC B cells though control of a metabolic program required for growth of these rapidly proliferating cells and their entry into the cell cycle. Thus, canonical NF-κB controls the GC B cell reaction through distinct and nonredundant mechanisms.

J. Exp. Med. (1 September 2014) doi:10.1084/jem.20132613