Visceral adipose tissue contributes to the generation of pro-inflammatory B cell subsets in aging mice

Abstract

Abstract Age-related decrease in B cell function is associated with chronic low-grade inflammation and increased pro-inflammatory mediators. This effect is also associated with an increase in visceral adipose tissue (VAT) and metabolic inflammation. Adipocyte-derived chemokines are involved in the chemotaxis of immune cells which infiltrate the VAT and contribute to the inflammatory process. To identify contributors to the phenotypic and functional changes observed in aged B cells, we undertook studies of B cells in the VAT. We recently analyzed immune cells infiltrating the VAT of obese C57BL/6 mice (age 12–24 months). We found macrophages, B cells and T cells in VAT in a ratio of 1:3:5. As to B cells, we measured the major B cell subsets and found higher percentages of pro-inflammatory (age-associated B cells, ABC) and less Follicular (FO) B cells in VAT as compared to spleen. B cells isolated from VAT express higher levels of inflammatory immune activation markers (TNF-α/IL-6/IL-8), significantly higher NF-kB activation and phospho-STAT3, and secrete higher amounts of Ig antibodies specific for fat antigens as compared to splenic B cells. To evaluate the ability of adipocytes from the VAT to promote inflammation and induce pro-inflammatory B cell subsets, we co-cultured adipocytes from the VAT with splenic B cells from the same mice. Results show that co-culture for 72 hrs significantly changed the relative percentages of the B cell subsets, leading to a higher percentage of ABC, similar to what we have observed in the fat. Moreover, we found that the adipocytes produce several pro-inflammatory chemokines. These results are the first to show a direct effect of adipocytes on pro-inflammatory B cells.