Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Heise, Nicole UNSPECIFIED UNSPECIFIED UNSPECIFIED De Silva, Nilushi S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Silva, Kathryn UNSPECIFIED UNSPECIFIED UNSPECIFIED Carette, Amanda UNSPECIFIED UNSPECIFIED UNSPECIFIED Simonetti, Giorgia UNSPECIFIED orcid.org/0000-0001-6954-969X UNSPECIFIED Pasparakis, Manolis UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED Klein, Ulf UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language C-REL; MICE LACKING; LYMPHOCYTE SURVIVAL; CLONAL SELECTION; IMMUNE-RESPONSE; FACTOR IRF4; T-CELLS; EXPRESSION; MEMORY; GENE Multiple languages Immunology; Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/42854