The role of BAFF overexpression in the loss of anti-dsDNA B cell tolerance
Item
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Title
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The role of BAFF overexpression in the loss of anti-dsDNA B cell tolerance
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Identifier
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d_2009_2013:45b7a675d06d:10684
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identifier
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10756
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Creator
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Thorn, Mitchell,
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Contributor
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Linda A. Spatz
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Date
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2010
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Language
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English
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Publisher
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City University of New York.
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Subject
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Cellular biology | autoimmunity | autoreactive antibodies | BAFF | B cells | B cell tolerance | systemic lupus erythematosus
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Abstract
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Overexpression of BAFF is believed to play an important role in Systemic Lupus Erythematosus and elevated levels of serum BAFF have been found in lupus patients. Excess BAFF also leads to overproduction of anti-dsDNA antibodies and a lupus-like syndrome in mice. In the present study, we use mice transgenic for the R4A-Cmu (IgMa) heavy chain of an anti-dsDNA antibody, to study the effects of BAFF overexpression on anti-dsDNA B-cell regulation. We observe that overexpression of BAFF promotes anti-dsDNA B cell maturation and secretion of antibody and enriches for transgenic anti-dsDNA B cells in the marginal zone and follicular splenic compartments. In addition, our data suggests that BAFF rescues a subset of anti-dsDNA B cells from a regulatory checkpoint in the transitional stage of development. The subset of B cells identified as transitional type 3 (T3) subset present in R4A-Cmu and R4A-Cmu/BAFF mice, exhibits an anergic phenotype and contains a high frequency of anti-dsDNA B cells. Our findings suggest that BAFF may enhance survival of this subset and promote anti-dsDNA Ab secretion in synergy with environmental stimuli such as CpG.
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Biology
