Prolactin rescues and primes autoreactive B cells directly and indirectly through dendritic cells in B6.Sle3 mice. (10th April 2013)

• Record Type: Journal Article
• Authors: Gonzalez, J.; Saha, S.; Peeva, E.
• Is Part Of: Clinical and experimental immunology. Volume 172:Number 2(2013:May)
• Page Start: 311
• Page End: 320
• Publication Date: 2013-04-10
• Subjects: Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12050
• Languages: English
• ISSNs: 0009-9104

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>The lupus susceptibility interval <italic>Sle3/5</italic> confers responsiveness to prolactin in C57BL/6 (B6) mice and hyperprolactinaemia induces a lupus‐like phenotype in B6.<italic>Sel3/5</italic> mice. In this study, the immunostimulatory effects of prolactin in B6 mice containing the <italic>Sle3</italic> portion of the <italic>Sel3/5</italic> interval (B6.<italic>Sle3</italic> mice) were dissected. Because of the <italic>Sle3</italic> interval's involvement in activation of myeloid cells, the effect of dendritic cells (DCs) from prolactin‐treated B6.<italic>Sle3</italic> mice on the phenotype of B6 mice was also evaluated. B cells from prolactin‐treated B6 and B6.<italic>Sle3</italic> mice and from B6 recipients of prolactin‐modulated DCs from B6<italic>.Sle3</italic> 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.<italic>Sle3</italic> 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<sup>b</sup>, and DCs and monocytes had higher levels of CD44 and B7·2 than placebo‐treated mice. Adoptive transfer of DCs from prolactin‐treated B6.<italic>Sle3</italic> 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.<italic>Sle3</italic> mice by promoting the survival, maturation and activation of autoreactive B cells, DCs and macrophages.</p> </abstract>