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

Autor: Stephanie Atencio, Shozo Izui, Brian L. Kotzin, Hirofumi Amano
Rok vydání: 2004
Předmět:
Genetic Markers
Lupus Erythematosus
Systemic/*genetics/*immunology/pathology
Immunology
Congenic
B-Lymphocyte Subsets
B-Lymphocyte Subsets/*cytology/*immunology/metabolism
Down-Regulation
Spleen
Antigens
CD29/biosynthesis/metabolism
Biology
ddc:616.07
urologic and male genital diseases
Animals
Newborn/genetics/immunology/metabolism
Lymphocyte Activation
Autoantibodies/biosynthesis
Mice
immune system diseases
medicine
Immunology and Allergy
Animals
Lupus Erythematosus
Systemic
Lymphocyte Count
skin and connective tissue diseases
B cell
Crosses
Genetic
Autoantibodies
Autoimmune disease
Systemic lupus erythematosus
Mice
Inbred NZB
Genetic Markers/*immunology
Integrin beta1
Cell Division/genetics/immunology
Autoantibody
Marginal zone
medicine.disease
Mice
Inbred C57BL
medicine.anatomical_structure
Animals
Newborn
Down-Regulation/immunology
Mice
Inbred NZB/*genetics
Spleen/*cytology/*immunology/metabolism
Peritoneum
Lymphocyte Activation/genetics
Nephritis
Peritoneum/cytology/immunology
Cell Division
Zdroj: Journal of Immunology, Vol. 172, No 7 (2004) pp. 4159-4166
ISSN: 0022-1767
Popis: The F1 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 × NZW)F1 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 × NZW)F1 mice develop elevated autoantibodies and nephritis similar to (NZB × NZW)F1 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 × NZW)F1 mice. Among the strains studied, B cell expression of β1 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.
Databáze: OpenAIRE
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