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

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 th...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2020-10, Vol.117 (40), p.24957-24963
Main Authors: Mayer, Christian T., Nieke, Jan P., Gazumyan, Anna, Cipolla, Melissa, Wang, Qiao, Oliveira, Thiago Y., Ramos, Victor, Monette, Sébastien, Li, Quan-Zhen, Gershwin, M. Eric, Kashkar, Hamid, Nussenzweig, Michel C.
Format: Article
Language:English
Subjects:
Animals
Antibodies
Antibodies, Antinuclear - immunology
Antinuclear antibodies
Apoptosis
Apoptosis - genetics
Apoptosis - immunology
Autoantibodies
Autoantibodies - immunology
Autoimmunity
Autoimmunity - genetics
Autoimmunity - immunology
B-Lymphocytes - immunology
Biological Sciences
Bone marrow
Genes, Immunoglobulin - genetics
Genes, Immunoglobulin - immunology
Germinal Center - immunology
Germinal centers
Humans
Immune Tolerance - genetics
Immunologic Memory - genetics
Immunologic Memory - immunology
Immunological memory
Immunological tolerance
Lymphocytes
Lymphocytes B
Memory cells
Mice
Mutation
Plasma cells
Plasma Cells - immunology
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2015372117