Bcl‐2 leads to expression of anti‐DNA B cells but no nephritis: a model for a clinical subset

P Kuo, MS Bynoe, C Wang… - European journal of …, 1999 - Wiley Online Library
P Kuo, MS Bynoe, C Wang, B Diamond
European journal of immunology, 1999Wiley Online Library
Transgenic mice expressing anti‐DNA antibodies have been extensively studied as a model
for understanding B cell regulation in systemic lupus erythematosus (SLE). BALB/c mice
transgenic for the R4A‐γ2b heavy chain of an anti‐double‐stranded DNA (dsDNA) antibody
produce two populations of high‐affinity anti‐dsDNA B cells, one deleted, and the other
anergized. We generated double‐transgenic BALB/c mice expressing both the R4A‐γ2b
heavy chain and the anti‐apoptotic bcl‐2 gene in the B cell compartment to study whether …
Abstract
Transgenic mice expressing anti‐DNA antibodies have been extensively studied as a model for understanding B cell regulation in systemic lupus erythematosus (SLE). BALB / c mice transgenic for the R4A‐γ2b heavy chain of an anti‐double‐stranded DNA (dsDNA) antibody produce two populations of high‐affinity anti‐dsDNA B cells, one deleted, and the other anergized. We generated double‐transgenic BALB / c mice expressing both the R4A‐γ2b heavy chain and the anti‐apoptotic bcl‐2 gene in the B cell compartment to study whether bcl‐2 overexpression differentially affected anergic and deleted B cells. The double‐transgenic mice (R4A / bcl‐2) express elevated serum titers of both high‐ and low‐affinity anti‐dsDNA antibodies and display rescue of autoreactive B cells that are normally either deleted or anergized. Despite the presence of anti‐dsDNA antibodies in their serum, R4A / bcl‐2‐transgenic mice do not develop nephritis, demonstrating that overexpression of bcl‐2 is not by itself sufficient to allow disease progression. This phenotype resembles that of some SLE patients who have high titers of anti‐DNA antibodies without nephritis.
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