title: Separation of the New Zealand Black genetic contribution to lupus from New Zealand Black determined expansions of marginal zone B and B1a cells.
abstract: The F(1) hybrid of New Zealand Black (NZB) and New Zealand White (NZW) mice develop an autoimmune disease similar to human systemic lupus erythematosus. Because NZB and (NZB x NZW)F(1) mice manifest expansions of marginal zone (MZ) B and B1a cells, it has been postulated that these B cell abnormalities are central to the NZB genetic contribution to lupus. Our previous studies have shown that a major NZB contribution comes from the Nba2 locus on chromosome 1. C57BL/6 (B6) mice congenic for Nba2 produce antinuclear Abs, and (B6.Nba2 x NZW)F(1) mice develop elevated autoantibodies and nephritis similar to (NZB x NZW)F(1) mice. We studied B cell populations of B6.Nba2 mice to better understand the mechanism by which Nba2 leads to disease. The results showed evidence of B cell activation early in life, including increased levels of serum IgM, CD69(+) B cells, and spontaneous IgM production in culture. However, B6.Nba2 compared with B6 mice had a decreased percentage of MZ B cells in spleen, and no increase of B1a cells in the spleen or peritoneum. Expansions of these B cell subsets were also absent in (B6.Nba2 x NZW)F(1) mice. Among the strains studied, B cell expression of beta(1) integrin correlated with differences in MZ B cell development. These results show that expansions of MZ B and B1a cells are not necessary for the NZB contribution to lupus and argue against a major role for these subsets in disease pathogenesis. The data also provide additional insight into how Nba2 contributes to lupus.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Atencio
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Amano
authors.forename: Shozo
authors.initials: S
authors.lastname: Izui
authors.forename: Brian L
authors.initials: BL
authors.lastname: Kotzin
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D015536:Down-Regulation / Q000276:immunology; D005819:Genetic Markers / Q000276:immunology*; D019012:Integrin beta1 / Q000096:biosynthesis / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB / Q000235:genetics*; D010537:Peritoneum / Q000166:cytology / Q000276:immunology; D013154:Spleen / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D005819:Genetic Markers; D019012:Integrin beta1