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PMID: 12070310 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Estrogen alters thresholds for B cell apoptosis and activation.

The Journal of clinical investigation ·Vol. 109 ·No. 12 ·2002-06-00 ·Pages 1625-33

Grimaldi CM, Cleary J, Dagtas AS, Moussai D, Diamond B

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.

MeSH Terms
Animals Antigens, CD/genetics Antigens, Differentiation, B-Lymphocyte/genetics Apoptosis B-Lymphocytes/cytology,drug effects,immunology,metabolism Cell Adhesion Molecules Cells, Cultured Estradiol/administration & dosage,pharmacology Estrogen Receptor alpha Estrogen Receptor beta Gene Expression Gene Expression Profiling Humans Intracellular Signaling Peptides and Proteins Lectins Lymphocyte Activation Mice Mice, Inbred BALB C Protein Tyrosine Phosphatase, Non-Receptor Type 6 Protein Tyrosine Phosphatases/genetics Proto-Oncogene Proteins c-bcl-2/genetics Receptors, Estrogen/genetics Sialic Acid Binding Ig-like Lectin 2 Vascular Cell Adhesion Molecule-1/genetics
Chemicals
Antigens, CD Antigens, Differentiation, B-Lymphocyte CD22 protein, human Cd22 protein, mouse Cell Adhesion Molecules Estrogen Receptor alpha Estrogen Receptor beta Intracellular Signaling Peptides and Proteins Lectins Proto-Oncogene Proteins c-bcl-2 Receptors, Estrogen Sialic Acid Binding Ig-like Lectin 2 Vascular Cell Adhesion Molecule-1 Estradiol PTPN6 protein, human Protein Tyrosine Phosphatase, Non-Receptor Type 6 Protein Tyrosine Phosphatases Ptpn6 protein, mouse
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Grimaldi Christine M
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Cleary James
Dagtas A Selma
Moussai Dariush
Diamond Betty
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI14873
Published
2002-06-00
Pages
1625-33
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC151010
Subset
IM
Grants
NIGMS NIH HHS · T32 GM007288 · United States
NIGMS NIH HHS · T32-GM07288 · United States
External Links
PubMed source DOI: 10.1172/JCI14873 PMC Full Text View journal details
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