Single cell transcriptomics identify AHR and CD9 as markers of CD14 +atypical B cells

Abstract

Abstract B lymphocytes are adaptive immune cells responsible for the production of antigen specific antibodies and the release of pro- and anti-inflammatory cytokines. Pro-inflammatory B cells, often termed atypical B cells (at B cell) are a heterogenous population of B lymphocytes associated with aging, infection, and autoimmunity. Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor important for xenobiotic metabolism. However, AHR is heavily implicated in immune cell differentiation as a regulator of cell fate decisions. at B cells are believed to represent an alternative B cell lineage but the role of AHR in at B cells is not known. We have reported that human, primary CD5 +innate-like B cells (ILB) are preferentially sensitive to modulation by AHR-activation compared to CD5 −B cells. CD5 +ILB are a heterogenous population of B cells enriched in IgM memory B cells, B1 B cells, marginal zone B cells, regulatory B cells, and at B cells. We used Single cell transcriptomics to elucidate AHR expression in human naïve, circulating CD19 +B cells isolated directly from PBMC and enriched for CD5 protein. We found that AHR expression correlated with expression of CD14and were enriched in a myeloid gene signature. These results were validated in isolated CD9 +B cells and PBMC. Further, CD14 expressing B cells were enriched in CD9 isolated cells and expressed higher CD11c and Tbet and lower IgD, markers of atypical B cells, compared to CD9 −B cells. These data suggest that CD9 and AHR are putative markers of CD14 +at B cells. (Supported by NIH grant P42ES004911) Supported by NIH grant P42ES004911