Abstract
Single-nucleotide polymorphisms and locus amplification fink the NF-kappa B 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.
Item Type: | Journal article |
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Faculties: | Biology > Department Biology II |
Subjects: | 500 Science > 570 Life sciences; biology |
ISSN: | 0021-9738 |
Language: | English |
Item ID: | 90330 |
Date Deposited: | 25. Jan 2022, 09:34 |
Last Modified: | 25. Jan 2022, 09:34 |