Bouma, GerbenCarter, Natalie ARecher, MikeMalinova, DessislavaAdriani, MarsilioNotarangelo, LuigiBurns, Siobhan OMauri, ClaudiaThrasher, Adrian J2014-12-022014Bouma, Gerben, Natalie A Carter, Mike Recher, Dessislava Malinova, Marsilio Adriani, Luigi D Notarangelo, Siobhan O Burns, Claudia Mauri, and Adrian J Thrasher. 2014. “Exacerbated experimental arthritis in Wiskott–Aldrich syndrome protein deficiency: Modulatory role of regulatory B cells.” European Journal of Immunology 44 (9): 2692-2702. doi:10.1002/eji.201344245. http://dx.doi.org/10.1002/eji.201344245.0014-2980http://nrs.harvard.edu/urn-3:HUL.InstRepos:13454832Patients deficient in the cytoskeletal regulator Wiskott–Aldrich syndrome protein (WASp) are predisposed to varied autoimmunity, suggesting it has an important controlling role in participating cells. IL-10-producing regulatory B (Breg) cells are emerging as important mediators of immunosuppressive activity. In experimental, antigen-induced arthritis WASp-deficient (WASp knockout [WAS KO]) mice developed exacerbated disease associated with decreased Breg cells and regulatory T (Treg) cells, but increased Th17 cells in knee-draining LNs. Arthritic WAS KO mice showed increased serum levels of B-cell-activating factor, while their B cells were unresponsive in terms of B-cell-activating factor induced survival and IL-10 production. Adoptive transfer of WT Breg cells ameliorated arthritis in WAS KO recipients and restored a normal balance of Treg and Th17 cells. Mice with B-cell-restricted WASp deficiency, however, did not develop exacerbated arthritis, despite exhibiting reduced Breg- and Treg-cell numbers during active disease, and Th17 cells were not increased over equivalent WT levels. These findings support a contributory role for defective Breg cells in the development of WAS-related autoimmunity, but demonstrate that functional competence in other regulatory populations can be compensatory. A properly regulated cytoskeleton is therefore important for normal Breg-cell activity and complementation of defects in this lineage is likely to have important therapeutic benefits.en-USArthritisImmune regulationRegulatory B cellsRegulatory T cellTh17 cellsWiskott–Aldrich syndrome proteinJournal Article2014-12-0210.1002/eji.201344245