Prolactin as a modulator of B cell function: implications for SLE.
Prolactin is not only a lactigenic hormone but also an immunomodulator involved in lymphocyte survival, activation and proliferation. There is increasing data implicating prolactin in autoimmunity, and specifically in SLE. Increased serum prolactin levels have been reported in lupus patients of both genders, and have been associated with accelerated disease expression and early mortality in lupus-prone mice. Furthermore, suppression of prolactin secretion with bromocriptine provides beneficial effects in murine lupus, and perhaps in some SLE patients as well. Treatment with prolactin that causes mild to moderate hyperprolactinemia, similar to that present in SLE patients, breaks tolerance and induces a lupus-like illness in non-spontaneously autoimmune mice with a susceptible genetic background. These immuno stimulatory effects of prolactin are mediated by a decrease in negative selection and the maturation of autoreactive B cells to the follicular subset. Consistent with the fact that follicular B cells are T cell dependent, CD4+ T cells are necessary for the prolactin-mediated break down of B cell tolerance. In mice, the effects of prolactin on the immune system are genetically determined, suggesting that only a subset of SLE patients are likely to have a prolactin-responsive disease. The manipulation of serum prolactin or, even more specifically, follicular B cells that are susceptible to the immuno stimulatory effects of prolactin, may provide novel therapeutic options for those SLE patients with a prolactin-modulated disease.
Peeva
Elena
E
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Rm. 405, Forch Building, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Venkatesh
Jeganathan
J
Michael
Daniel
D
Diamond
Betty
B
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001971:Bromocriptine / Q000627:therapeutic use; D018491:Dopamine Agonists / Q000627:therapeutic use; D006801:Humans; D006966:Hyperprolactinemia / Q000276:immunology / Q000503:physiopathology; D007108:Immune Tolerance; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology*; D051379:Mice; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000097:blood / Q000276:immunology*
D018491:Dopamine Agonists; D001971:Bromocriptine; D011388:Prolactin