Prolactin modulates the naive B cell repertoire.
Prolactin is a peptide hormone produced by the anterior pituitary gland that is critical in lactation. Prolactin can also be produced by lymphocytes, and both B and T cells express prolactin receptors. These findings have suggested that prolactin has immunomodulatory functions. Studies in spontaneously autoimmune hosts have demonstrated a role for prolactin in augmenting autoreactivity. We chose to analyze prolactin effects on anti-DNA B cells in nonspontaneously autoimmune female BALB/c mice transgenic for the heavy chain of an anti-DNA antibody. Treatment with prolactin for 4 weeks induced a lupus-like phenotype with an increased number of transgene-expressing B cells, elevated serum anti-DNA antibody titers, and glomerular immunoglobulin deposits. Prolactin caused a decrease in the population of transitional B cells and an increase in mature follicular and marginal zone B cells. The DNA-reactive B cells had a follicular cell phenotype. Anti-DNA hybridomas demonstrated that prolactin alters selection of the naive B cell repertoire. The expansion and activation of anti-DNA B cells in prolactin-treated R4A-gamma2b BALB/c mice was dependent on the presence of CD4(+) T cells. Finally, treatment with prolactin was unable to break tolerance in R4A-gamma2b transgenic C57Bl/6 mice, suggesting that responsiveness of the immune system to prolactin is genetically determined.
Peeva
Elena
E
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Michael
Daniel
D
Cleary
James
J
Rice
Jeffrey
J
Chen
Xian
X
Diamond
Betty
B
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D019013:CD40 Antigens / Q000096:biosynthesis; D004247:DNA / Q000276:immunology; D005260:Female; D006825:Hybridomas / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011388:Prolactin / Q000494:pharmacology*
D000974:Antibodies, Antinuclear; D019013:CD40 Antigens; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D011388:Prolactin; D004247:DNA