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  c-Rel gain in B cells drives germinal center reactions and autoantibody production

Kober-Hasslacher, M., Oh-Strauss, H., Kumar, D., Soberon, V., Diehl, C., Lech, M., et al. (2020). c-Rel gain in B cells drives germinal center reactions and autoantibody production. JOURNAL OF CLINICAL INVESTIGATION, 130(6), 3270-3286. doi:10.1172/JCI124382.

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 Creators:
Kober-Hasslacher, Maike1, Author           
Oh-Strauss, Hyunju2, Author
Kumar, Dilip1, Author           
Soberon, Valeria2, Author
Diehl, Carina2, Author
Lech, Maciej2, Author
Engleitner, Thomas2, Author
Katab, Eslam2, Author
Fernandez-Saiz, Jvanesa2, Author
Piontek, Guido2, Author
Li, Hongwei2, Author
Menze, Bjorn2, Author
Ziegenhain, Christoph2, Author
Enard, Wolfgang2, Author
Rad, Roland2, Author
Boettcher, Jan P.2, Author
Anders, Hans-Joachim2, Author
Rudelius, Martina2, Author
Schmidt-Supprian, Marc1, Author           
Affiliations:
1Schmidt-Supprian, Marc / Molecular Immunology and Signaltransduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565167              
2external, ou_persistent22              

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Free keywords: GENOME-WIDE ASSOCIATION; TRANSCRIPTION FACTOR; CYCLE PROGRESSION; MICE LACKING; GENE; EXPRESSION; DIFFERENTIATION; SUSCEPTIBILITY; DISEASE; PROLIFERATION
 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.

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Language(s): eng - English
 Dates: 2020
 Publication Status: Published in print
 Pages: 17
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000544332600055
DOI: 10.1172/JCI124382
 Degree: -

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Title: JOURNAL OF CLINICAL INVESTIGATION
Source Genre: Journal
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Publ. Info: 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA : AMER SOC CLINICAL INVESTIGATION INC
Pages: - Volume / Issue: 130 (6) Sequence Number: - Start / End Page: 3270 - 3286 Identifier: ISSN: 0021-9738