ARID3a-Expressing SLE Naive B Cells Exhibit an Activated Phenotype and Can be Identified by Transient Expression of a New Surface Marker
We found numbers of ARID3a (AT-Rich Interaction Domain 3a) -expressing Blymphocytes from patients with systemic lupus erythematosus (SLE) are associated withincreased disease activity. ARID3a-expressing circulating healthy naive B cells are rare whilenaive B cells isolated from SLE patients show dramatic increases in ARID3a expression. Wefound that in vitro stimulation of B lymphocytes from healthy individuals induced ARID3a in asubset of activated naive B cells and in IgD - CD27 - double negative B cells previously associatedwith autoimmunity. Single cell RNA-seq of isolated naive B cells from ten SLE patients withvarying frequencies of ARID3a-expressing cells revealed that ARID3a-associated genesincluded activation markers. Moreover, our data identified the unexpected expression of thesurface marker CD68 at both the transcript and protein level with ARID3a in activated subsets ofnaive B cells. Inhibition of ARID3a in stimulated B cell cultures blocked induction of activatednaive B cells with CD68 expression. Together, these data identify ARID3a and CD68 asmarkers of naive B cell precursors associated with autoimmunity in SLE.