Characterization of functional and phenotypic heterogeneity of autoimmune-associated B cells in systemic lupus erythematosus (SLE)

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Presentation Time: 04:30 PM - 04:45 PM
Abstract ID: 4612 - B

Presenting Author:
Sun Jung Kim , Associate Professor at Feinstein Inst. for Med. Res., Northwell Hlth., Zucker Sch. of Med. at Hofstra/Northwell

Abstract:

Autoimmune/age associated B cells (ABCs) have been associated with autoimmune diseases including SLE. ABCs are found in lymphoid organ and affected tissue, such as kidney in lupus nephritic patients. Now it is accepted that ABCs are heterogenous and functionally distinct, but the function of ABC or ABC subsets in SLE has not been fully defined. To characterize the function and heterogeneity of ABCs, we performed single cell RNA-seq with VDJ-seq from SLE patients. Within the ABCs (CD19+ CD11c+CXCR5-CD21-), we found 4 subpopulations. Trajectory analysis does not provide strong evidence of transition from ABCs into the plasma cells. In vitro, ABCs are not as efficient as memory B cells to differentiate into plasma cells. Instead, we found ABC as a strong antigen presenting cells (APCs); thy express co-stimulation molecules, secrete cytokines that induce T-cell activation and differentiation. Co-culture of ABCs with T cells induce a follicular helper T (Tfh) phenotype in naïve T-cells. We also expand our observations made in SLE patients to lupus mouse model; lupus ABCs are efficient APCs with antigen uptake and production of pro-inflammatory cytokine, IL-1b. IL-1b-producing proinflammatory subset of ABCs are increased in autoantibody-positive lupus mice. ABCs have elevated fatty acid contents and a blocking of fatty acid uptake reduces inflammatory phenotypes in ABCs. Overall, we found a unique mechanism of antigen uptake process and pro-inflammatory function of ABCs in SLE.