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, 2022 03.
Article
en En
| MEDLINE
| ID: mdl-34384840
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos B
/
Proteína del Síndrome de Wiskott-Aldrich
/
Neutropenia
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Allergy Clin Immunol
Año:
2022
Tipo del documento:
Article