Wiskott-Aldrich Syndrome protein deficiency perturbs the homeostasis of B-cell compartment in humans

Maria Carmina Castiello, Marita Bosticardo, Francesca Pala, Marco Catucci, Nicolas Chamberlain, Menno C. Van Zelm, Gertjan J. Driessen, Malgorzata Pac, Ewa Bernatowska, Samantha Scaramuzza, Alessandro Aiuti, Aisha V. Sauer, Elisabetta Traggiai, Eric Meffre, Anna Villa, Mirjam Van der Burg

Research output: Contribution to journalArticlepeer-review


Wiskott-Aldrich Syndrome protein (WASp) regulates the cytoskeleton in hematopoietic cells and mutations in its gene cause the Wiskott-Aldrich Syndrome (WAS), a primary immunodeficiency with microthrombocytopenia, eczema and a higher susceptibility to develop tumors. Autoimmune manifestations, frequently observed in WAS patients, are associated with an increased risk of mortality and still represent an unsolved aspect of the disease. B cells play a crucial role both in immune competence and self-tolerance and defects in their development and function result in immunodeficiency and/or autoimmunity. We performed a phenotypical and molecular analysis of central and peripheral B-cell compartments in WAS pediatric patients. We found a decreased proportion of immature B cells in the bone marrow correlating with an increased presence of transitional B cells in the periphery. These results could be explained by the defective migratory response of WAS B cells to SDF-1α, essential for the retention of immature B cells in the BM. In the periphery, we observed an unusual expansion of CD21low B-cell population and increased plasma BAFF levels that may contribute to the high susceptibility to develop autoimmune manifestations in WAS patients. WAS memory B cells were characterized by a reduced invivo proliferation, decreased somatic hypermutation and preferential usage of IGHV4-34, an immunoglobulin gene commonly found in autoreactive B cells. In conclusion, our findings demonstrate that WASp-deficiency perturbs B-cell homeostasis thus adding a new layer of immune dysregulation concurring to the increased susceptibility to develop autoimmunity in WAS patients.

Original languageEnglish
Pages (from-to)42-50
Number of pages9
JournalJournal of Autoimmunity
Publication statusPublished - 2014


  • Autoimmunity
  • B lymphocyte
  • B-cell activating factor (BAFF)
  • Immunoglobulin repertoire
  • Primary immunodeficiency
  • Wiskott-aldrich syndrome

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)


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