Antigen-induced apoptotic death of ly-1 b cells responsible for autoimmune disease in transgenic mice

ABSTRACT STUDIES on transgenic mice expressing immunoglobulins against self-antigens1–6 have shown that self-tolerance is maintained by active elimination (clonal deletion)1–3,7, functional

inactivation (clonal anergy)4,5,8 of self-reactive B cells, or a combination of both6. We have established and characterized a transgenic mouse line expressing an anti-erythrocyte

autoantibody6. In contrast to other autoantibody transgenic lines, about 50% of the animals of this transgenic line suffer from autoimmune disease, indicating a loss of self-tolerance. Here

we show that peritoneal Ly-1 B cells (also known as B-l cells9) are responsible for this autoimmune disease in our transgenic mice. A few self-reactive Ly-1 B cells that have somehow escaped

the deletion mechanism expand in the peritoneum because of the absence of self-antigen. These Ly-1 B cells are eliminated _in vivo_ by apoptosis once exposed to self-antigen. On the basis

of these results we propose a novel autoantibody production mechanism whereby self-reactive B cellssequestered in compartments free of self-antigens may survive, proliferate and be activated

for generation of pathogenic auto-antibodies in autoimmune diseases. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution

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about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS ANTIGEN PRESENTATION BY B CELLS ENABLES EPITOPE SPREADING ACROSS AN MHC

BARRIER Article Open access 31 October 2023 PERIPHERAL APOPTOSIS AND LIMITED CLONAL DELETION DURING PHYSIOLOGIC MURINE B LYMPHOCYTE DEVELOPMENT Article Open access 01 June 2024 B

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AUTHORS AND AFFILIATIONS * Department of Medical Chemistry, Kyoto University, Sakyo-ku, Kyoto, 606, Japan Masao Murakami, Takeshi Tsubata, Masaya Okamoto & Tasuku Honjo * Second

Department of Internal Medicine, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606, Japan Masao Murakami, Shunichi Kumagai & Hiroo Imura * Center for Molecular Biology and

Genetics, Kyoto University, Sakyo-ku, Kyoto, 606, Japan Akira Shimizu & Tasuku Honjo Authors * Masao Murakami View author publications You can also search for this author inPubMed Google

Scholar * Takeshi Tsubata View author publications You can also search for this author inPubMed Google Scholar * Masaya Okamoto View author publications You can also search for this author

inPubMed Google Scholar * Akira Shimizu View author publications You can also search for this author inPubMed Google Scholar * Shunichi Kumagai View author publications You can also search

for this author inPubMed Google Scholar * Hiroo Imura View author publications You can also search for this author inPubMed Google Scholar * Tasuku Honjo View author publications You can

also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Murakami, M., Tsubata, T., Okamoto, M. _et al._

Antigen-induced apoptotic death of Ly-1 B cells responsible for autoimmune disease in transgenic mice. _Nature_ 357, 77–80 (1992). https://doi.org/10.1038/357077a0 Download citation *

Received: 22 January 1992 * Accepted: 25 March 1992 * Issue Date: 07 May 1992 * DOI: https://doi.org/10.1038/357077a0 SHARE THIS ARTICLE Anyone you share the following link with will be able

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