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Overactive WASp in X-linked neutropenia leads to aberrant B-cell division and accelerated plasma cell generation
- Publication Year :
- 2022
- Publisher :
- MOSBY-ELSEVIER, 2022.
-
Abstract
- 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. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY vol:149 issue:3 pages:1069-1084 ispartof: location:United States status: published
- Subjects :
- Neutropenia
Wiskott–Aldrich syndrome
Plasma Cells
Immunology
Naive B cell
macromolecular substances
Plasma cell
Biology
primary immunodeficiency
plasma cells
Affinity maturation
Mice
X-linked neutropenia
medicine
Animals
Humans
Immunology and Allergy
B cell
B-Lymphocytes
B cells
Cell growth
Germinal center
Genetic Diseases, X-Linked
WASp
medicine.disease
Molecular biology
Immunoglobulin A
medicine.anatomical_structure
Immunoglobulin class switching
germinal center
actin
Cell Division
Wiskott-Aldrich Syndrome Protein
IgA
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....f0ef37ac865c60929f5c0a816547960f