| First Author | Almaden JV | Year | 2016 |
| Journal | Blood | Volume | 127 |
| Issue | 10 | Pages | 1276-86 |
| PubMed ID | 26773039 | Mgi Jnum | J:232643 |
| Mgi Id | MGI:5779751 | Doi | 10.1182/blood-2014-10-606988 |
| Citation | Almaden JV, et al. (2016) B-cell survival and development controlled by the coordination of NF-kappaB family members RelB and cRel. Blood 127(10):1276-86 |
| abstractText | Targeted deletion of BAFF causes severe deficiency of splenic B cells. BAFF-R is commonly thought to signal to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB)-inducing kinase dependent noncanonical NF-kappaB RelB. However, RelB-deficient mice have normal B-cell numbers. Recent studies showed that BAFF also signals to the canonical NF-kappaB pathway, and we found that both RelB and cRel are persistently activated, suggesting BAFF signaling coordinates both pathways to ensure robust B-cell development. Indeed, we report now that combined loss of these 2 NF-kappaB family members leads to impaired BAFF-mediated survival and development in vitro. Although single deletion of RelB and cRel was dispensable for normal B-cell development, double knockout mice displayed an early B-cell developmental blockade and decreased mature B cells. Despite disorganized splenic architecture in Relb(-/-)cRel(-/-) mice, generation of mixed-mouse chimeras established the developmental phenotype to be B-cell intrinsic. Together, our results indicate that BAFF signals coordinate both RelB and cRel activities to ensure survival during peripheral B-cell maturation. |
