Germinal center B cell maintenance and differentiation are controlled by distinct NF-?B transcription factor subunits.

ABSTRACT: Germinal centers (GCs) are the sites where memory B cells and plasma cells producing high-affinity antibodies are generated during T cell-dependent immune responses. The molecular control of GC B cell maintenance and differentiation remains incompletely understood. Activation of the NF-?B signaling pathway has been implicated; however, the distinct roles of the individual NF-?B transcription factor subunits are unknown. We report that GC B cell-specific deletion of the NF-?B subunits c-REL or RELA, which are both activated by the canonical NF-?B pathway, abolished the generation of high-affinity B cells via different mechanisms acting at distinct stages during the GC reaction. c-REL deficiency led to the collapse of established GCs immediately after the formation of dark and light zones at day 7 of the GC reaction and was associated with the failure to activate a metabolic program that promotes cell growth. Conversely, RELA was dispensable for GC maintenance but essential for the development of GC-derived plasma cells due to impaired up-regulation of BLIMP1. These results indicate that activation of the canonical NF-?B pathway in GC B cells controls GC maintenance and differentiation through distinct transcription factor subunits. Our findings have implications for the role of NF-?B in GC lymphomagenesis.

SUBMITTER: Heise N 

PROVIDER: S-EPMC4172226 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature