Universität zu Köln

Mayer, Christian T., Nieke, Jan P., Gazumyan, Anna, Cipolla, Melissa ORCID: 0000-0001-8156-2512, Wang, Qiao, Oliveira, Thiago Y., Ramos, Victor ORCID: 0000-0001-7353-3420, Monette, Sebastien, Li, Quan-Zhen, Gershwin, M. Eric, Kashkar, Hamid and Nussenzweig, Michel C. (2020). An apoptosis-dependent checkpoint for autoimmunity in memory B and plasma cells. Proc. Natl. Acad. Sci. U. S. A., 117 (40). S. 24957 - 24964. WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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Abstract

B lymphocytes acquire self-reactivity as an unavoidable byproduct of antibody gene diversification in the bone marrow and in germinal centers (GCs). Autoreactive B cells emerging from the bone marrow are silenced in a series of well-defined checkpoints, but less is known about how self-reactivity that develops by somatic mutation in GCs is controlled. Here, we report the existence of an apoptosis-dependent tolerance checkpoint in post-GC B cells. Whereas defective GC B cell apoptosis has no measurable effect on autoantibody development, disruption of post-GC apoptosis results in accumulation of autoreactive memory B cells and plasma cells, antinuclear antibody production, and autoimmunity. The data presented shed light on mechanisms that regulate immune tolerance and the development of autoantibodies.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mayer, Christian T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nieke, Jan P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gazumyan, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Cipolla, Melissa UNSPECIFIED orcid.org/0000-0001-8156-2512 UNSPECIFIED Wang, Qiao UNSPECIFIED UNSPECIFIED UNSPECIFIED Oliveira, Thiago Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ramos, Victor UNSPECIFIED orcid.org/0000-0001-7353-3420 UNSPECIFIED Monette, Sebastien UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Quan-Zhen UNSPECIFIED UNSPECIFIED UNSPECIFIED Gershwin, M. Eric UNSPECIFIED UNSPECIFIED UNSPECIFIED Kashkar, Hamid UNSPECIFIED UNSPECIFIED UNSPECIFIED Nussenzweig, Michel C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-315663
DOI:	10.1073/pnas.2015372117
Journal or Publication Title:	Proc. Natl. Acad. Sci. U. S. A.
Volume:	117
Number:	40
Page Range:	S. 24957 - 24964
Date:	2020
Publisher:	NATL ACAD SCIENCES
Place of Publication:	WASHINGTON
ISSN:	0027-8424
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SOMATIC HYPERMUTATION; EXPRESSION; ANTIBODIES; ANTIGEN; AUTOANTIBODIES; ELIMINATION; HOMEOSTASIS; LYMPHOCYTE; REDEMPTION; RESPONSES Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31566