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Separation of the New Zealand Black genetic contribution to lupus from New Zealand Black determined expansions of marginal zone B and B1a cells

Atencio, Stephanie
Kotzin, B. L.
Published in Journal of Immunology. 2004, vol. 172, no. 7, p. 4159-4166
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.
Keywords AnimalsAnimals, Newborn/genetics/immunology/metabolismAntigens, CD29/biosynthesis/metabolismAutoantibodies/biosynthesisB-Lymphocyte Subsets/*cytology/*immunology/metabolismCell Division/genetics/immunologyCrosses, GeneticDown-Regulation/immunologyGenetic Markers/*immunologyLupus Erythematosus, Systemic/*genetics/*immunology/pathologyLymphocyte Activation/geneticsLymphocyte CountMiceMice, Inbred C57BLMice, Inbred NZB/*geneticsPeritoneum/cytology/immunologySpleen/*cytology/*immunology/metabolism
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PMID: 15034028
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