| First Author | He M | Year | 2022 |
| Journal | J Allergy Clin Immunol | Volume | 149 |
| Issue | 3 | Pages | 1069-1084 |
| PubMed ID | 34384840 | Mgi Jnum | J:321936 |
| Mgi Id | MGI:7256246 | Doi | 10.1016/j.jaci.2021.07.033 |
| Citation | He M, et al. (2022) Overactive WASp in X-linked neutropenia leads to aberrant B-cell division and accelerated plasma cell generation. J Allergy Clin Immunol 149(3):1069-1084 |
| abstractText | BACKGROUND: B-cell affinity maturation in germinal center relies on regulated actin dynamics for cell migration and cell-to-cell communication. Activating mutations in the cytoskeletal regulator Wiskott-Aldrich syndrome protein (WASp) cause X-linked neutropenia (XLN) with reduced serum level of IgA. OBJECTIVE: We investigated the role of B cells in XLN pathogenesis. METHODS: We examined B cells from 6 XLN patients, 2 of whom had novel R268W and S271F mutations in WASp. By using immunized XLN mouse models that carry the corresponding patient mutations, WASp L272P or WASp I296T, we examined the B-cell response. RESULTS: XLN patients had normal naive B cells and plasmablasts, but reduced IgA(+) B cells and memory B cells, and poor B-cell proliferation. On immunization, XLN mice had a 2-fold reduction in germinal center B cells in spleen, but with increased generation of plasmablasts and plasma cells. In vitro, XLN B cells showed reduced immunoglobulin class switching and aberrant cell division as well as increased production of immunoglobulin-switched plasma cells. CONCLUSIONS: Overactive WASp predisposes B cells for premature differentiation into plasma cells at the expense of cell proliferation and immunoglobulin class switching. |
