Estrogen alters thresholds for B cell apoptosis and activation.
Journal: 2002/July - Journal of Clinical Investigation
ISSN: 0021-9738
Abstract:
Estrogen is thought to contribute to the increased frequency of autoimmune disorders occurring in females, but a molecular basis for its effects on autoimmunity remains to be elucidated. We have shown previously that estrogen leads to the survival and activation of autoreactive cells in the naive repertoire. To identify the molecular pathways involved in B cell tolerance, we sought to identify genes that are differentially regulated by estrogen in mouse B cells. Several genes involved in B cell activation and survival, including cd22, shp-1, bcl-2, and vcam-1, were upregulated by estrogen in B cells. We found that overexpression of CD22 and SHP-1 in B cells decreased B cell receptor signaling. Estrogen receptors alpha and beta are expressed on B cells and are functional, since they can directly upregulate expression of CD22, SHP-1, and Bcl-2. Estrogen treatment protected isolated primary B cells from B cell receptor-mediated apoptosis. These results suggest that estrogen induces a genetic program that alters survival and activation of B cells in a B cell-autonomous fashion and thus skews the naive immune system toward autoreactivity.
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J Clin Invest 109(12): 1625-1633

Estrogen alters thresholds for B cell apoptosis and activation

Department of Microbiology and Immunology, and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA
Address correspondence to: Betty Diamond, Department of Microbiology and Immunology, 1300 Morris Park Avenue, Room 405, Forchheimer Building, Bronx, New York 10461, USA. Phone: (718) 430-4081; Fax: (718) 430-8711; E-mail: ude.uy.mocea@dnomaid.
Address correspondence to: Betty Diamond, Department of Microbiology and Immunology, 1300 Morris Park Avenue, Room 405, Forchheimer Building, Bronx, New York 10461, USA. Phone: (718) 430-4081; Fax: (718) 430-8711; E-mail: ude.uy.mocea@dnomaid.
Received 2001 Dec 17; Accepted 2002 May 14.

Abstract

Estrogen is thought to contribute to the increased frequency of autoimmune disorders occurring in females, but a molecular basis for its effects on autoimmunity remains to be elucidated. We have shown previously that estrogen leads to the survival and activation of autoreactive cells in the naive repertoire. To identify the molecular pathways involved in B cell tolerance, we sought to identify genes that are differentially regulated by estrogen in mouse B cells. Several genes involved in B cell activation and survival, including cd22, shp-1, bcl-2, and vcam-1, were upregulated by estrogen in B cells. We found that overexpression of CD22 and SHP-1 in B cells decreased B cell receptor signaling. Estrogen receptors α and β are expressed on B cells and are functional, since they can directly upregulate expression of CD22, SHP-1, and Bcl-2. Estrogen treatment protected isolated primary B cells from B cell receptor–mediated apoptosis. These results suggest that estrogen induces a genetic program that alters survival and activation of B cells in a B cell–autonomous fashion and thus skews the naive immune system toward autoreactivity.

Abstract

Acknowledgments

This work was supported by grants from the NIH (to B. Diamond) and the New York Chapter of the Arthritis Foundation (to C.M. Grimaldi). J. Cleary is funded by NIH Medical Scientist Training Program grant T32-GM07288.

Acknowledgments

Footnotes

Christine M. Grimaldi and James Cleary contributed equally to this work.

Footnotes

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