title: Age-Dependent Defects of Regulatory B Cells in Wiskott-Aldrich Syndrome Gene Knockout Mice.
abstract: The Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by recurrent infections, thrombocytopenia, eczema, and high incidence of malignancy and autoimmunity. The cellular mechanisms underlying autoimmune complications in WAS have been extensively studied; however, they remain incompletely defined. We investigated the characteristics of IL-10-producing CD19+CD1dhighCD5+ B cells (CD1dhighCD5+ Breg) obtained from Was gene knockout (WKO) mice and found that their numbers were significantly lower in these mice compared to wild type (WT) controls. Moreover, we found a significant age-dependent reduction of the percentage of IL-10-expressing cells in WKO CD1dhighCD5+ Breg cells as compared to age-matched WT control mice. CD1dhighCD5+ Breg cells from older WKO mice did not suppress the in vitro production of inflammatory cytokines from activated CD4+ T cells. Interestingly, CD1dhighCD5+ Breg cells from older WKO mice displayed a basal activated phenotype which may prevent normal cellular responses, among which is the expression of IL-10. These defects may contribute to the susceptibility to autoimmunity with age in patients with WAS.
authors.affiliation: Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Yokoyama
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Yoshizaki
authors.affiliation: Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Simon
authors.affiliation: Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Martha R
authors.initials: MR
authors.lastname: Kirby
authors.affiliation: Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Stacie M
authors.initials: SM
authors.lastname: Anderson
authors.affiliation: Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America; Division of Immunology and Allergy, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Fabio
authors.initials: F
authors.lastname: Candotti
mesh_terms: D000375:Aging; D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D055610:Antigens, CD1d / Q000378:metabolism; D060151:B-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018956:CD5 Antigens / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D016753:Interleukin-10 / Q000032:analysis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D014923:Wiskott-Aldrich Syndrome / Q000378:metabolism / Q000473:pathology*
chemical_list: D018941:Antigens, CD19; D055610:Antigens, CD1d; D018956:CD5 Antigens; D016207:Cytokines; D016753:Interleukin-10