@article{bff23d0ff8cf4960b25b00c37e1d9500,
title = "An apoptosis-dependent checkpoint for autoimmunity in memory B and plasma cells",
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.",
keywords = "Antinuclear antibodies, Apoptosis, Autoantibody, B lymphocytes",
author = "Mayer, {Christian T.} and Nieke, {Jan P.} and Anna Gazumyan and Melissa Cipolla and Qiao Wang and Oliveira, {Thiago Y.} and Victor Ramos and S{\'e}bastien Monette and Li, {Quan Zhen} and Gershwin, {M. Eric} and Hamid Kashkar and Nussenzweig, {Michel C.}",
note = "Funding Information: ACKNOWLEDGMENTS. We thank Thomas Eisenreich for help with mouse colony management; Daniel Yost for antibody production; Kai-Hui Yao for technical help; Kalsang Chhosphel and Kristie Gordon for cell sorting; Davide Robbiani, Mila Jankovic, Harald Hartweger, and Julia Merkenschlager, and all members of the M.C.N. laboratory for discussion. We further thank Dr. Chingwen Yang, the Gene Targeting Resource Center, and Drs. Alison North and Christina Pyrgaki from the Bio-imaging Resource Center of The Rockefeller University. This work was supported by NIH Grant 5R37 AI037526 and NIH Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery Grant 1UM1AI144462-01 (to M.C.N.), and by the German Research Foundation SFB-1403–414786233 (to H.K.). M.C.N. is a HHMI Investigator. S.M. and the Laboratory of Comparative Pathology were supported in part by National Cancer Institute Grant P30 CA008748. The Bio-imaging Resource Center of The Rockefeller University was supported by the Empire State Stem Cell Fund through New York State Department of Health Contract C023046. Opinions expressed here are solely those of the author and do not necessarily reflect those of the Empire State Stem Cell Fund, the NYSDOH, or the State of New York. Publisher Copyright: {\textcopyright} 2020 National Academy of Sciences. All rights reserved.",
year = "2020",
month = oct,
day = "6",
doi = "10.1073/pnas.2015372117",
language = "English (US)",
volume = "117",
pages = "24957--24963",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "40",
}