T-bet+ B cells accumulate in adipose tissue and exacerbate metabolic disorder during obesity

Abstract

Obesity is accompanied by inflammation in adipose tissue, impaired glucose tolerance, and changes in adipose leukocyte populations. These studies of adipose tissue from humans and mice revealed that increased frequencies of T-bet⁺ B cells in adipose tissue depend on invariant NKT cells and correlate with weight gain during obesity. Transfer of B cells enriched for T-bet⁺ cells exacerbates metabolic disorder in obesity, while ablation of Tbx21 specifically in B cells reduces serum IgG2c levels, inflammatory cytokines, and inflammatory macrophages in adipose tissue, ameliorating metabolic symptoms. Furthermore, transfer of serum or purified IgG from HFD mice restores metabolic disease in T-bet⁺ B cell-deficient mice, confirming T-bet⁺ B cell-derived IgG as a key mediator of inflammation during obesity. Together, these findings reveal an important pathological role for T-bet⁺ B cells that should inform future immunotherapy design in type 2 diabetes and other inflammatory conditions.

Keywords: B cells; CD11c(+) T-bet(+) B cells; IgG2c; adipose tissue; glucose intolerance; iNKT cells; inflammation; metabolic disorder; obesity; type 2 diabetes.