Genes associated with ARID3a expression in B Lymphocytes from Systemic Lupus Erythematosus patients

Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease characterized by overproduction of autoantibodies by B cells and the loss of tolerance to nucleic acids. Our previous studies demonstrated that AT-rich interacting domain 3a (ARID3a), a DNA-binding protein associated with immunoglobulin transcription, is more abundant in SLE B lymphocytes than in healthy control B cells. ARID3a expression in SLE patient blood occurred in naïve B cell subsets which do not express ARID3a in healthy controls. Importantly, increased numbers of ARID3a+ B cells in SLE correlated with increased disease activity in patients. Our recent data indicated that ARID3a is critical for the expression of the key inflammatory cytokine, interferon-alpha (IFNa), in B cells and other blood cells. ARID3a+ B cells appear to denote a new kind of B effector cell that can induce IFNa expression in other cell types. We hypothesize that ARID3a is an important contributor to increased disease activity in SLE patients. Therefore, it is important to better define the characteristics of these cells. ARID3a is bimodally expressed, such that only a fraction of the cells within any B cell subset express ARID3a at a given time. Our current studies took advantage of this bimodal expression using single-cell technology to perform RNA-seq analyses of ARID3a+ and ARID3a− SLE B cells to identify differentially expressed genes associated with ARID3a. To date, ARID3a expression is correlated with innate immune response genes and epigenetic regulators. We predict these studies will be informative regarding how ARID3a expression contributes to disease pathogenesis in patients with SLE, and will provide novel information defining a new subset of effector B cells.