Autoantibodies are a prominent feature of the BXSB-Yaa mouse model of systemic lupus erythematosus. Previous studies showed that these mice express high levels of IL-21, a cytokine produced by follicular T helper cells known to drive GC reactions. To determine if IL-21 has a role in disease pathogenesis, we generated mice deficient in expression of the IL21 receptor (IL-21R). Remarkably, IL-21R-deficient BXSB-Yaa mice were essentially normal with none of the autoimmune or other features that normally characterize that strain. The development of severe SLE-like autoimmunity in this strain was found to be normally restrained by the activity of CD8 T cell-NK cell regulatory axis that appears to restrict the activity of T follicular helper cells. La is an autoantigen and antibodies directed against it are found in patients with Sjogren's syndrome and systemic lupus erythematosus. We evaluated a possible role of Lain B cell development by generating a conditional. We found that La is absolutely required for B cell development as La-deficient mice had no B cells. We also studied the role played by ARF-BP1 in governing life or death decisions in B cells. Mice deficient in ARF-BP1 had many abnormalities in B cell development associated with increased expression of p52 and decreased expression of Myc. We found that enforced expression of Myc in the B cell lineage corrected almost all the B cell abnormalities seen in ARF-BP1-deficint mice.

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8
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2014
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