Cutting edge: lupus susceptibility interval Sle3/5 confers responsiveness to prolactin in C57BL/6 mice.
Prolactin is of interest in the pathogenesis of systemic lupus erythematosus (SLE) because almost 25% of SLE patients display hyperprolactinemia, and serum prolactin correlates with disease activity in some patients. Furthermore, hyperprolactinemia causes early mortality in lupus-prone mice and induces a lupus-like phenotype in nonspontaneously autoimmune mice. We show here that the immunomodulatory effects of prolactin are genetically determined; hyperprolactinemia breaks B cell tolerance and causes a lupus-like serology in BALB/c mice expressing a transgene encoding the H chain of an anti-DNA Ab but not in C57BL/6 transgenic mice. In C57BL/6 mice that express both the H chain transgene and the lupus susceptibility interval Sle3/5, prolactin induces increased serum titers of anti-DNA Ab and glomerular Ig depositions. The increase in costimulation due to prolactin-mediated up-regulation of both CD40 on B cells and CD40L on T cells would appear to play a central role in lupus induction in this model.
Peeva
Elena
E
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Gonzalez
Juana
J
Hicks
Ruthmarie
R
Diamond
Betty
B
D000279:Administration, Cutaneous; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000096:biosynthesis; D023201:CD40 Ligand / Q000096:biosynthesis; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D008822:Mice, Transgenic; D011388:Prolactin / Q000008:administration & dosage* / Q000097:blood / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D019013:CD40 Antigens; D023201:CD40 Ligand; D011388:Prolactin