[HTML][HTML] Bromocriptine restores tolerance in estrogen-treated mice

E Peeva, C Grimaldi, L Spatz… - The Journal of clinical …, 2000 - Am Soc Clin Investig
E Peeva, C Grimaldi, L Spatz, B Diamond
The Journal of clinical investigation, 2000Am Soc Clin Investig
Estrogen can modulate autoimmunity in certain models of systemic lupus erythematosus.
Recently, we have shown that it can mediate survival and activation of anti-DNA B cells in a
mouse transgenic for the heavy chain of a pathogenic anti-DNA antibody. To identify
whether estrogen effects reflect increased prolactin secretion, we characterized B-cell
autoreactivity in transgenic mice given both bromocriptine (an inhibitor of prolactin secretion)
and estradiol. Treatment of mice with estradiol plus bromocriptine led to reduced titers of anti …
Estrogen can modulate autoimmunity in certain models of systemic lupus erythematosus. Recently, we have shown that it can mediate survival and activation of anti-DNA B cells in a mouse transgenic for the heavy chain of a pathogenic anti-DNA antibody. To identify whether estrogen effects reflect increased prolactin secretion, we characterized B-cell autoreactivity in transgenic mice given both bromocriptine (an inhibitor of prolactin secretion) and estradiol. Treatment of mice with estradiol plus bromocriptine led to reduced titers of anti-DNA antibodies and diminished IgG deposition in kidneys compared with treatment with estradiol alone. However, mice treated with estradiol plus bromocriptine showed an expansion of transgene-expressing B cells and enhanced Bcl-2 expression, similar to those of estradiol-treated mice. We identified anergic high-affinity anti-DNA B cells in mice treated with estradiol plus bromocriptine, and we showed by molecular analysis of anti-DNA hybridomas that their B cells derive from a naive repertoire. Thus, the estradiol-induced breakdown in B-cell tolerance can be abrogated by bromocriptine, which induces anergy in the high-affinity DNA-reactive B cells. These studies demonstrate that some of the effects of estrogen on naive autoreactive B cells require the presence of prolactin and, thus, suggest potential therapeutic interventions in lupus.
The Journal of Clinical Investigation