Gene Expression Analysis of Dual-? B cells in Lupus

Autoreactive B cells expressing two different immunoglobulin light chains are present in elevated numbers in a subset of systemic lupus erythematosus patients and in MRL and MRL/lpr mouse models of lupus. Using RNAseq and genetic pathway analyses together with in vitro studies we demonstrate a role for TLR and IFN signaling in MRL/lpr dual-? B cell expansion and/or activation. Dual-? cells also showed increased expression of co-receptors used for T cell cognate interaction as well as enrichment of pathways involved in their signaling. Overall, our studies identify molecular pathways involved in the enrichment of dual-reactive effector B cells and reveal potential targets for their selective ablation in autoimmunity. Overall design: Examination of sorted single and dual-? B cells from either the marginal zone or the follicles in the spleen of MRL/lpr lupus-prone mice.