An apoptosis-dependent checkpoint for autoimmunity in memory B and plasma cells

Christian T. Mayer, Jan P. Nieke, Anna Gazumyan, Melissa Cipolla, Qiao Wang, Thiago Y. Oliveira, Victor Ramos, Sébastien Monette, Quan Zhen Li, M. Eric Gershwin, Hamid Kashkar, Michel C. Nussenzweig

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)24957-24963
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number40
DOIs
StatePublished - Oct 6 2020

Keywords

  • Antinuclear antibodies
  • Apoptosis
  • Autoantibody
  • B lymphocytes

ASJC Scopus subject areas

  • General

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