Estrogen alters thresholds for B cell apoptosis and activation
Christine M. Grimaldi, … , Dariush Moussai, Betty Diamond
Christine M. Grimaldi, … , Dariush Moussai, Betty Diamond
Published June 15, 2002
Citation Information: J Clin Invest. 2002;109(12):1625-1633. https://doi.org/10.1172/JCI14873.
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Article Immunology

Estrogen alters thresholds for B cell apoptosis and activation

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.

Authors

Christine M. Grimaldi, James Cleary, A. Selma Dagtas, Dariush Moussai, Betty Diamond

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Figure 3

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Detection of ERs in B cell subsets. Bone marrow cells and splenocytes we...
Detection of ERs in B cell subsets. Bone marrow cells and splenocytes were isolated, and cell suspensions from three mice were pooled together and stained with Ab’s to detect ER-α or ER-β plus Ab’s to detect developmental surface markers. Bone marrow pro/pre cells were identified as B220lo/sIgM– and immature as B220lo/sIgM–. Splenic transitional B cells were identified as B220lo/CD24hi, mature as B220int/CD24lo, and germinal center as CD19+/GL7+. The experiment was performed three times on a total of 13 mice, and representative histograms of stage-specific expression are shown. Specific staining is represented by a solid line, and the isotype-matched control is represented by a dashed line.