Phenotypic perturbation of B cells in the Wiskott-Aldrich syndrome.
Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency/platelet disease due to mutations of WASP, a cytoskeletal regulatory protein of blood cells. Patients exhibit a range of immune defects generally attributed to defective T-cell function, including poor response to immunization, skewed immunoglobulin isotypes, eczema, recurrent infections, autoimmune disease and increased frequency of malignancies. Here we show a deficit of total B-cells in WAS patients of various ages and identify phenotypic perturbations involving complement receptors and CD27. Whereas B-cells of normal healthy donors are overwhelmingly CD21/CD35-positive, B-cells expressing these receptors are significantly reduced in number in WAS patients, and their paucity may cause suboptimal antigen capture and presentation. The frequencies of IgD(-) and IgG(+) patient B-cells were not different from healthy donors (although absolute numbers were decreased), indicating that isotype switching is occurring. In contrast, the frequency of cells positive for CD27, the marker of post germinal centre B-cells, was significantly decreased even among isotype-switched cells, and B-cells resembling germinal centre progenitors (CD10(+)CD27(-)CD38(bright)) were more frequent in adult patients, suggesting impaired germinal centre maturation/differentiation. The documentation of these phenotypic perturbations and deficit of total cells suggest that defects intrinsic to B-cells contribute to the impaired humoral immunity that characterizes this disease.
Park
J Y
JY
The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA.
Shcherbina
A
A
Rosen
F S
FS
Prodeus
A P
AP
Remold-O'Donnell
E
E
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005434:Flow Cytometry; D006801:Humans; D007072:Immunoglobulin D / Q000032:analysis; D018655:Lymphocyte Count; D015260:Neprilysin / Q000276:immunology; D011506:Proteins / Q000235:genetics*; D011951:Receptors, Complement / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*; D014923:Wiskott-Aldrich Syndrome / Q000276:immunology*; D051316:Wiskott-Aldrich Syndrome Protein
D007072:Immunoglobulin D; D011506:Proteins; D011951:Receptors, Complement; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein; D015260:Neprilysin