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Published on: December 9, 2013
Estrogen alters thresholds for B cell apoptosis and activation
Christine M Grimaldi1, James Cleary, A Selma Dagtas
1Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
The Journal of Clinical Investigation
|June 19, 2002
Summary
Estrogen promotes autoimmunity in females by increasing the survival and activation of autoreactive B cells. This occurs through estrogen receptors directly upregulating genes that alter B cell signaling and apoptosis.
Area of Science:
- Immunology
- Endocrinology
- Molecular Biology
Background:
- Estrogen is linked to higher rates of autoimmune diseases in females.
- The molecular mechanisms underlying estrogen's influence on autoimmunity are not fully understood.
- Previous work indicated estrogen promotes autoreactive cell survival and activation.
Purpose of the Study:
- To identify genes differentially regulated by estrogen in mouse B cells.
- To elucidate the molecular pathways estrogen uses to affect B cell tolerance and autoimmunity.
- To investigate the role of estrogen receptors alpha and beta in B cells.
Main Methods:
- Gene expression analysis in mouse B cells treated with estrogen.
- Overexpression studies of CD22 and SHP-1 in B cells.
- Assessment of B cell receptor signaling and apoptosis.
- Analysis of estrogen receptor expression and function on B cells.
Main Results:
- Estrogen upregulated genes like CD22, SHP-1, Bcl-2, and VCAM-1 in B cells.
- Overexpression of CD22 and SHP-1 reduced B cell receptor signaling.
- Estrogen receptors alpha and beta are functional on B cells, directly upregulating target genes.
- Estrogen protected primary B cells from apoptosis mediated by B cell receptor signaling.
Conclusions:
- Estrogen induces a genetic program in B cells that enhances their survival and activation.
- This estrogen-driven program operates in a B cell-autonomous manner.
- Estrogen skews the naive immune system towards autoreactivity, potentially explaining its association with autoimmune diseases in females.
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