| First Author | Kober-Hasslacher M | Year | 2020 |
| Journal | J Clin Invest | Volume | 130 |
| Issue | 6 | Pages | 3270-3286 |
| PubMed ID | 32191641 | Mgi Jnum | J:313591 |
| Mgi Id | MGI:6757576 | Doi | 10.1172/JCI124382 |
| Citation | Kober-Hasslacher M, et al. (2020) c-Rel gain in B cells drives germinal center reactions and autoantibody production. J Clin Invest 130(6):3270-3286 |
| abstractText | Single-nucleotide polymorphisms and locus amplification link the NF-kappaB transcription factor c-Rel to human autoimmune diseases and B cell lymphomas, respectively. However, the functional consequences of enhanced c-Rel levels remain enigmatic. Here, we overexpressed c-Rel specifically in mouse B cells from BAC-transgenic gene loci and demonstrate that c-Rel protein levels linearly dictated expansion of germinal center B (GCB) cells and isotype-switched plasma cells. c-Rel expression in B cells of otherwise c-Rel-deficient mice fully rescued terminal B cell differentiation, underscoring its critical B cell-intrinsic roles. Unexpectedly, in GCB cells transcription-independent regulation produced the highest c-Rel protein levels among B cell subsets. In c-Rel-overexpressing GCB cells this caused enhanced nuclear translocation, a profoundly altered transcriptional program, and increased proliferation. Finally, we provide a link between c-Rel gain and autoimmunity by showing that c-Rel overexpression in B cells caused autoantibody production and renal immune complex deposition. |
