Wiskott-Aldrich syndrome protein deficiency leads to reduced B-cell adhesion, migration, and homing, and a delayed humoral immune response.
The Wiskott-Aldrich syndrome protein (WASp) is mutated in the severe immunodeficiency disease Wiskott-Aldrich syndrome (WAS). The function of B cells and the physiologic alterations in WAS remain unclear. We show that B cells from WAS patients exhibited decreased motility and had reduced capacity to migrate, adhere homotypically, and form long protrusions after in vitro culture. WASp-deficient murine B cells also migrated less well to chemokines. Upon antigen challenge, WASp-deficient mice mounted a reduced and delayed humoral immune response to both T-cell-dependent and -independent antigens. This was at least in part due to deficient migration and homing of B cells. In addition, the germinal center reaction was reduced in WASp-deficient mice. Thus, WASp is crucial for optimal B-cell responses and plays a pivotal role in the primary humoral immune response.
Westerberg
Lisa
L
Karolinska Institutet, Department of Cell and Molecular Biology, Medical Nobel Institute, Box 285, SE-171 77 Stockholm, Sweden.
Larsson
Malin
M
Hardy
Samantha J
SJ
Fernández
Carmen
C
Thrasher
Adrian J
AJ
Severinson
Eva
E
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D002448:Cell Adhesion / Q000276:immunology*; D002449:Cell Aggregation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D013154:Spleen / Q000276:immunology; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics; D051316:Wiskott-Aldrich Syndrome Protein
D011506:Proteins; C495767:WAS protein, human; C495768:Was protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein