ARID3a-Expressing Naïve B Cells in SLE have an Activated Phenotype and Transiently Express Surface CD68

Numbers of ARID3a ( AT - R ich Interaction D omain 3a ) -expressing B lymphocytes from patients with systemic lupus erythematosus (SLE) are associated with increased disease activity. Normally, ARID3a-expressing circulating naïve B cells are rare, but in SLE naïve B cells dramatically increase ARID3a expression. We found that in vitro stimulation of B lymphocytes from healthy individuals with a cocktail of cytokines and agonists induced ARID3a in a subset of activated naïve B cells and in IgD ^- CD27 ^- double negative B cells previously associated with autoimmunity. Single cell RNA-seq of isolated naïve B cells from ten SLE patients, with varying frequencies of ARID3a-expressing cells, revealed that ARID3a-associated genes included activation markers. Moreover, our data revealed the unexpected co-expression of the scavenger receptor CD68 with ARID3a, at both the transcript and protein level, in activated subsets of naïve B cells. Inhibition of ARID3a in stimulated B cell cultures blocked naïve B cell activation and CD68 expression. Together, these data identify ARID3a and CD68 as markers of naïve B cell precursors associated with autoimmunity in SLE.