Prolactin (PRL) plays an important role in modulating the immune response. In B cells, PRL enhances antibody production, including antibodies with self-specificity. In this study, our aims were to determine the level of PRL receptor expression during bone-marrow B-cell development and to assess whether the presence of high PRL serum concentrations influences absolute numbers of developing populations and disease outcome in lupus-prone murine models. We observed that the PRL-receptor is expressed in early bone-marrow B-cell; the expression in lupus-prone mice, which had the highest level of expression in pro-B cells and immature cells, differed from that in wild-type mice. These expression levels did not significantly change in response to hyperprolactinemia; however, populations of pro-B and immature cells from lupus-prone strains showed a decrease in the absolute numbers of cells with high PRL-receptor expression in response to PRL. Because immature self-reactive B cells are constantly being eliminated, we assessed the expression of survival factor BIRC5, which is more highly expressed in both pro-B and immature B-cells in response to PRL and correlates with the onset of disease. These results identify an important role of PRL in the early stages of the B-cell maturation process: PRL may promote the survival of self-reactive clones. 1. Introduction Prolactin (PRL) is predominantly produced by the lactotropic cells of the anterior pituitary gland. However, it is also generated in extrapituitary sites, such as immune, decidual, mammary, epithelial, and fat cells [1–3]. PRL has multiple regulatory roles in reproduction, development, growth, osmosis, metabolism of carbohydrates and lipids, and the immune response. The PRL receptor is a member of the cytokine receptor superfamily [3–5]. Different isoforms of the PRL receptor have been found to be generated by alternative splicing at the 3′ end and variation in the intracellular domain length [3, 5, 6]. The PRL receptor is expressed in many immune cell types, mainly B cells, and also T cells, monocytes, macrophages, natural killer (NK) cells, and thymic epithelial cells [7, 8], and its activation induces transcriptional programs involved in various cellular functions such as proliferation, differentiation, and cytokine production. Hence, PRL has been implicated as a modulator of both cellular and humoural immunity [8–11]. Elevated serum PRL levels have been reported in several autoimmune diseases, including systemic lupus erythematosus (SLE) [12–14]. SLE is an autoimmune rheumatic disease. Serum samples from
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