Heise, Nicole, De Silva, Nilushi S., Silva, Kathryn, Carette, Amanda, Simonetti, Giorgia ORCID: 0000-0001-6954-969X, Pasparakis, Manolis ORCID: 0000-0002-9870-0966 and Klein, Ulf (2014). Germinal center B cell maintenance and differentiation are controlled by distinct NF-kappa B transcription factor subunits. J. Exp. Med., 211 (10). S. 2103 - 2119. NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-9538

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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-kappa B signaling pathway has been implicated; however, the distinct roles of the individual NF-kappa B transcription factor subunits are unknown. We report that GC B cell-specific deletion of the NF-kappa B subunits c-REL or RELA, which are both activated by the canonical NF-kappa 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-kappa 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-kappa B in GC lymphomagenesis.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Heise, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Silva, Nilushi S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Silva, KathrynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carette, AmandaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simonetti, GiorgiaUNSPECIFIEDorcid.org/0000-0001-6954-969XUNSPECIFIED
Pasparakis, ManolisUNSPECIFIEDorcid.org/0000-0002-9870-0966UNSPECIFIED
Klein, UlfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-428549
DOI: 10.1084/jem.20132613
Journal or Publication Title: J. Exp. Med.
Volume: 211
Number: 10
Page Range: S. 2103 - 2119
Date: 2014
Publisher: ROCKEFELLER UNIV PRESS
Place of Publication: NEW YORK
ISSN: 1540-9538
Language: English
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
C-REL; MICE LACKING; LYMPHOCYTE SURVIVAL; CLONAL SELECTION; IMMUNE-RESPONSE; FACTOR IRF4; T-CELLS; EXPRESSION; MEMORY; GENEMultiple languages
Immunology; Medicine, Research & ExperimentalMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/42854

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