Prolactin alters the mechanisms of B cell tolerance induction

Subhrajit Saha, Juana Gonzalez, Gabriel Rosenfeld, Harold Keiser, Elena Peeva

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Objective. Autoimmune diseases predominantly affect women, suggesting that female sex hormones may play a role in the pathogenesis of such diseases. We have previously shown that persistent mild-to-moderate elevations in serum prolactin levels induce a break in self tolerance in mice with a BALB/c genetic background. The aim of this study was to evaluate the effects of hyperprolactinemia on the mechanisms of B cell tolerance induction. Methods. Effects of prolactin on splenic B cell subsets were studied in female BALB/c mice. B cell receptor (BCR)-mediated apoptosis and proliferation of transitional B cells were analyzed by flow cytometry. Expression of apoptotic genes was examined by microarrays and real-time polymerase chain reaction analysis. B cells coexpressing κ/λ light chains were assessed by flow cytometry and immunohistochemistry. Activation status of transitional type 3 (T3) B cells was evaluated by BCR-induced calcium influx studies. Results. BCR-mediated apoptosis of the T1 B cell subset, a major checkpoint for negative selection of autoreactive specificities, was decreased in prolactin-treated mice. Microarray studies indicated that this event may be mediated by the prolactin-induced upregulation of the antiapoptotic gene interferon-γ receptor type II and down-regulation of the proapoptotic gene Trp63. Prolactin treatment also altered the amount of receptor editing, as indicated by the increased number of transitional B cells coexpressing κ/λ light chains. Additionally, hyperprolactinemia modified the level of B cell anergy by increasing the degree of BCR-induced calcium influx in the T3 B cells. Conclusion. Persistently elevated serum prolactin levels interfere with B cell tolerance induction by impairing BCR-mediated clonal deletion, deregulating receptor editing, and decreasing the threshold for activation of anergic B cells, thereby promoting autoreactivity.

Original languageEnglish (US)
Pages (from-to)1743-1752
Number of pages10
JournalArthritis and Rheumatism
Volume60
Issue number6
DOIs
StatePublished - Jun 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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    Saha, S., Gonzalez, J., Rosenfeld, G., Keiser, H., & Peeva, E. (2009). Prolactin alters the mechanisms of B cell tolerance induction. Arthritis and Rheumatism, 60(6), 1743-1752. https://doi.org/10.1002/art.24500