• Anna S Wilhelmson, Marta Lantero Rodriguez, Alexandra Stubelius, Per Fogelstrand, Inger Johansson, Matthew B Buechler, Steve Lianoglou, Varun N Kapoor, Maria E Johansson, Johan B Fagman, Amanda Duhlin, Prabhanshu Tripathi, Alessandro Camponeschi, Bo T Porse, Antonius G Rolink, Hans Nissbrandt, Shannon J Turley, Hans Carlsten, Inga-Lill Mårtensson, Karlsson Mikael C I MCI http://orcid.org/0000-0001-5582-614X Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, SE-171 77, Stoc, and Åsa Tivesten.
• Wallenberg Laboratory for Cardiovascular and Metabolic Research, Institute of Medicine, University of Gothenburg, Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45, Gothenburg, Sweden.
• Nat Commun. 2018 May 25; 9 (1): 2067.

AbstractTestosterone deficiency in men is associated with increased risk for autoimmunity and increased B cell numbers through unknown mechanisms. Here we show that testosterone regulates the cytokine BAFF, an essential survival factor for B cells. Male mice lacking the androgen receptor have increased splenic B cell numbers, serum BAFF levels and splenic Baff mRNA. Testosterone deficiency by castration causes expansion of BAFF-producing fibroblastic reticular cells (FRCs) in spleen, which may be coupled to lower splenic noradrenaline levels in castrated males, as an α-adrenergic agonist decreases splenic FRC number in vitro. Antibody-mediated blockade of the BAFF receptor or treatment with the neurotoxin 6-hydroxydopamine revert the increased splenic B cell numbers induced by castration. Among healthy men, serum BAFF levels are higher in men with low testosterone. Our study uncovers a previously unrecognized regulation of BAFF by testosterone and raises important questions about BAFF in testosterone-mediated protection against autoimmunity.

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