Antibody Reactivity of B Cells in Lupus Patients with Increased Disease Activity and ARID3a Expression
AbstractEarlier studies showed that the DNA-binding protein, Bright/ARID3a bound to a subset of human and mouse immunoglobulin heavy chain promoters where it enhanced expression. Indeed, mice with transgenic expression of ARID3a in all B lymphocytes have expanded MZ B cells and produce anti-nuclear antibodies (ANAs). Consistent with our findings in mice, we observed that human systemic lupus erythematosus (SLE) patients had expanded numbers of peripheral blood ARID3a+ B cells that were associated with increased disease activity (p = 0.0038). We hypothesized that ARID3a+ naïve B cells would eventually produce autoantibodies, explaining associations between ARID3a expression and disease activity in lupus. Unlike healthy controls, ARID3a was expressed in the naïve B cell population in SLE patients, and we hypothesized that these might represent expansions of autoreactive cells. Therefore, monoclonal antibodies were generated from single-sorted naïve B cells derived from patients with normal (ARID3aN) and high (ARID3aH) numbers of ARID3a+ B cells. We found that ARID3a expression did not correlate with autoantibody expression. Furthermore, measures of antigen specificities of autoreactive antibodies did not reveal skewing toward particular proteins. These data suggest that the association of increased disease activity in SLE with numbers of ARID3a+ B lymphocytes may be mediated by an antibody-independent mechanism. View Full-Text
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Ward, J.M.; James, J.A.; Zhao, Y.D.; Webb, C.F. Antibody Reactivity of B Cells in Lupus Patients with Increased Disease Activity and ARID3a Expression. Antibodies 2015, 4, 354-368.
Ward JM, James JA, Zhao YD, Webb CF. Antibody Reactivity of B Cells in Lupus Patients with Increased Disease Activity and ARID3a Expression. Antibodies. 2015; 4(4):354-368.Chicago/Turabian Style
Ward, Julie M.; James, Judith A.; Zhao, Yan D.; Webb, Carol F. 2015. "Antibody Reactivity of B Cells in Lupus Patients with Increased Disease Activity and ARID3a Expression." Antibodies 4, no. 4: 354-368.