title: Prolactin rescues and primes autoreactive B cells directly and indirectly through dendritic cells in B6.Sle3 mice.
abstract: The lupus susceptibility interval Sle3/5 confers responsiveness to prolactin in C57BL/6 (B6) mice and hyperprolactinaemia induces a lupus-like phenotype in B6.Sel3/5 mice. In this study, the immunostimulatory effects of prolactin in B6 mice containing the Sle3 portion of the Sel3/5 interval (B6.Sle3 mice) were dissected. Because of the Sle3 interval's involvement in activation of myeloid cells, the effect of dendritic cells (DCs) from prolactin-treated B6.Sle3 mice on the phenotype of B6 mice was also evaluated. B cells from prolactin-treated B6 and B6.Sle3 mice and from B6 recipients of prolactin-modulated DCs from B6.Sle3 mice were tested for DNA-reactivity and resistance to B cell receptor (BCR)-mediated apoptosis. The expression of co-stimulatory molecules on lymphocytes and myeloid cells was also evaluated. In prolactin-treated B6.Sle3 mice, transitional type 2 B cells increased while type 1 B cells decreased as a consequence of prolactin-induced resistance to BCR-mediated apoptosis leading to the survival of DNA-reactive B cells. Follicular B cells from prolactin-treated mice expressed increased levels of CD40, B7·2 and IA(b), and DCs and monocytes had higher levels of CD44 and B7·2 than placebo-treated mice. Adoptive transfer of DCs from prolactin-treated B6.Sle3 mice to B6 recipients demonstrated the intrinsic ability of prolactin-modulated DCs to induce a development of lupus-like characteristics in B6 mice. Based on these results, prolactin accelerates the breakdown of immune tolerance in B6.Sle3 mice by promoting the survival, maturation and activation of autoreactive B cells, DCs and macrophages.
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Gonzalez
authors.forename: S
authors.initials: S
authors.lastname: Saha
authors.forename: E
authors.initials: E
authors.lastname: Peeva
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005921:Glomerulonephritis / Q000276:immunology; D018960:Hyaluronan Receptors / Q000378:metabolism; D006966:Hyperprolactinemia / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D011388:Prolactin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism
chemical_list: D019013:CD40 Antigens; D018960:Hyaluronan Receptors; D011947:Receptors, Antigen, B-Cell; D011388:Prolactin