title: Regulatory B cells (B10 cells) have a suppressive role in murine lupus: CD19 and B10 cell deficiency exacerbates systemic autoimmunity.
abstract: B cells play critical roles in the pathogenesis of lupus. To examine the influence of B cells on disease pathogenesis in a murine lupus model, New Zealand Black and New Zealand White F(1) hybrid (NZB/W) mice were generated that were deficient for CD19 (CD19(-/-) NZB/W mice), a B cell-specific cell surface molecule that is essential for optimal B cell signal transduction. The emergence of anti-nuclear Abs was significantly delayed in CD19(-/-) NZB/W mice compared with wild type NZB/W mice. However, the pathologic manifestations of nephritis appeared significantly earlier, and survival was significantly reduced in CD19(-/-) NZB/W mice compared with wild type mice. These results demonstrate both disease-promoting and protective roles for B cells in lupus pathogenesis. Recent studies have identified a potent regulatory B cell subset (B10 cells) within the rare CD1d(hi)CD5(+) B cell subset of the spleen that regulates acute inflammation and autoimmunity through the production of IL-10. In wild type NZB/W mice, the CD1d(hi)CD5(+)B220(+) B cell subset that includes B10 cells was increased by 2.5-fold during the disease course, whereas CD19(-/-) NZB/W mice lacked this CD1d(hi)CD5(+) regulatory B cell subset. However, the transfer of splenic CD1d(hi)CD5(+) B cells from wild type NZB/W mice into CD19(-/-) NZB/W recipients significantly prolonged their survival. Furthermore, regulatory T cells were significantly decreased in CD19(-/-) NZB/W mice, but the transfer of wild type CD1d(hi)CD5(+) B cells induced T regulatory cell expansion in CD19(-/-) NZB/W mice. These results demonstrate an important protective role for regulatory B10 cells in this systemic autoimmune disease.
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: Rei
authors.initials: R
authors.lastname: Watanabe
authors.forename: Nobuko
authors.initials: N
authors.lastname: Ishiura
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nakashima
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kuwano
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okochi
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Tamaki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Tedder
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujimoto
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000502:physiology; D018941:Antigens, CD19 / Q000235:genetics* / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D007165:Immunosuppression Therapy; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D018345:Mice, Knockout
chemical_list: D000974:Antibodies, Antinuclear; D018941:Antigens, CD19