Abstract 16572: Single-Cell Transcriptomics Revealed Distinct B Cell Activation and Repression States in Obese Adipose Tissue

Obesity increases risk of several disease states including type-2 diabetes, arthritis, and cardiovascular disease. B cell dysfunction within visceral adipose tissue (AT) has been demonstrated to be a driving force towards insulin resistance, but the AT B cells (ATBs) responsible have not been well identified or characterized. We sought to elucidate the cellular changes occurring in ATBs during obesity that will confer obesity’s comorbidities using the single cell RNA sequencing technique. Consistent with previous studies, we observed a significant change in the B cell compartment composition in obese AT compared to the control lean ATBs. As expected, the majority of lean ATBs were naïve cells, characterized by several factors including moderate expression of transcription factor Pax5 and low BCR activation. Further cell function annotation identified two distinct states with increased proportions of obese ATBs, which were revealed by differential gene expression analysis to be either activated towards antibody producing or in a state of repression. The first state was characterized by an upregulation of several genes in B cell receptor (BCR) signaling and subsequent transcription factors such as Blk, Cd19, Pax5, Slamf7, and Cr2, suggesting activation. Such activation status is concomitant with high Ighm and increasing Ighd levels in the same cell population. Interestingly, we also observed a distinct B subtype that was also enriched in obese ATBs. These ATBs displayed low immunoglobulin production, low BCR associated proteins, low transcription factors, and high Pdcd1lg2, mouse homolog to human PD-L2, the programmed cell death ligand used in B cell repression. Further characterization of these newly identified ATB states under healthy or obese conditions suggested a significant change in B cell polarized action in obesity. The impact of these diversified ATB on other immune cells and the adipocyte actions and their cell-cell interaction will be further analyzed using our original bioinformatic programs. A high resolution of ATBs action in obesity will provide critical information to develop new therapeutic/prevention strategies against obesity induced health risk.