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PMID: 10694576 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Estrogen up-regulates Bcl-2 and blocks tolerance induction of naive B cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 6 ·2000-03-14 ·Pages 2703-8

Bynoe MS, Grimaldi CM, Diamond B

Abstract

Sex hormones are presumed to contribute to sexual dimorphism in the immune system. Estrogen, in particular, has been suggested to predispose women to systemic lupus erythematosus. We report here that estradiol (E(2)) can break B cell tolerance and induce a lupus-like phenotype in nonautoimmune mice transgenic for the heavy chain of a pathogenic anti-DNA antibody. E(2) treatment resulted in a rise in anti-DNA serum titers and in Ig deposition in renal glomeruli. ELISPOT analysis confirmed a significant increase in the number of high-affinity anti-DNA antibody-secreting B cells in the spleens of E(2)-treated mice. Hybridomas generated from E(2)-treated mice express high-affinity, unmutated anti-DNA antibodies, indicating that naive B cells that are normally deleted or anergized are rescued from tolerance induction. Finally, immunohistochemical studies revealed increased Bcl-2 expression in splenic B cells of E(2)-treated mice. These data demonstrate that estrogen interferes with tolerance induction of naive autoreactive B cells and that the presence of these B cells in the periphery is associated with up-regulation of Bcl-2.

MeSH Terms
Amino Acid Sequence Animals Antibody Affinity B-Lymphocytes/immunology,metabolism Base Sequence Bone Marrow Cells/metabolism Cell Line DNA/metabolism Enzyme-Linked Immunosorbent Assay Estradiol/blood,pharmacology Female Flow Cytometry Hybridomas/immunology Immune Tolerance Immunoglobulin kappa-Chains/genetics Kidney/immunology Mice Mice, Inbred BALB C Mice, Transgenic Molecular Sequence Data Proto-Oncogene Proteins c-bcl-2/genetics,metabolism Sequence Homology, Amino Acid Sequence Homology, Nucleic Acid Spleen/metabolism Up-Regulation
Chemicals
Immunoglobulin kappa-Chains Proto-Oncogene Proteins c-bcl-2 Estradiol DNA
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Bynoe M S
Departments of Microbiology and Immunology and Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Grimaldi C M
Diamond B
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.040577497
Published
2000-03-14
Pages
2703-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC15993
Subset
IM
Databases
GENBANK
AF217806
External Links
PubMed source DOI: 10.1073/pnas.040577497 PMC Full Text View journal details
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