Distinct PD-1 hiCD4+ T helper cell populations promote CD11c+ T-bet+ B cell expansion in liver and spleen during obesity.

Abstract

Abstract Obesity is associated with increased deposition of fat in ectopic tissues, such as within the liver and visceral adipose depots, including the omentum and mesentery. Increased visceral fat is an accompanying feature of the metabolic syndrome and is associated with increased end-organ damage in NAFLD. Emerging evidence implicates intrahepatic B cells in the progression of NAFLD, and increased number of proinflammatory B cells have been found in the steatotic livers of HFD-fed mice. Our preliminary studies demonstrate accumulation of inflammatory T-bet+ CD11c+ B cells in the subcutaneous adipose tissue of obese humans and perigonadal adipose tissue of mice on HFD. We now extend those findings into other sites of ectopic fat deposition to determine the obesity-related changes in T-bet+ B cell frequencies in the liver, omenta, and MAT. Flow cytometry identified increased frequencies of T-bet+ B cells in the spleen and livers, but not visceral adipose, of HFD mice. Furthermore, HFD-associated expansion of T-bet+ B cells in the spleen and liver correlated with a rise of T FHand T PHfrequencies, respectively. Future studies will determine the mechanism of tissue-specific T and B cell interactions associated with obesity-induced chronic inflammation. B.T.E. is supported by the NIH award (K12GM111726). T.H. is supported by a postdoctoral fellowship from the Swedish Research Council. This study was supported by NIH R01 AI32798-01A1 and the Voelcker Fund Young Investigator Awards (E.A.L).