Exacerbated experimental arthritis in Wiskott-Aldrich syndrome protein deficiency: Modulatory role of regulatory B cells

Gerben Bouma*, Natalie A. Carter, Mike Recher, Dessislava Malinova, Marsilio Adriani, Luigi D. Notarangelo, Siobhan O. Burns, Claudia Mauri, Adrian J. Thrasher

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)
17 Downloads (Pure)


Patients deficient in the cytoskeletal regulatorWiskott-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-cellactivating 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 inWAS 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 Bregcell activity and complementation of defects in this lineage is likely to have important therapeutic benefits.

Original languageEnglish
Pages (from-to)2692-2702
JournalEuropean Journal of Immunology
Issue number9
Early online date15 Jul 2014
Publication statusPublished - 15 Sept 2014
Externally publishedYes


  • Arthritis
  • Immune regulation
  • Regulatory B cells
  • Regulatory T cell
  • Th17 cells
  • Wiskott-aldrich syndrome protein

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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