Adipose Natural Regulatory B Cells Negatively Control Adipose Tissue Inflammation

Distinct B cell populations, designated regulatory B (B_reg) cells, are known to restrain immune responses associated with autoimmune diseases. Additionally, obesity is known to induce local inflammation within adipose tissue that contributes to systemic metabolic abnormalities, but the underlying mechanisms that modulate adipose inflammation remain poorly understood. We identified B_reg cells that produce interleukin-10 constitutively within adipose tissue. B cell-specific Il10 deletion enhanced adipose inflammation and insulin resistance in diet-induced obese mice, whereas adoptive transfer of adipose tissue B_reg cells ameliorated those effects. Adipose environmental factors, including CXCL12 and free fatty acids, support B_reg cell function, and B_reg cell fraction and function were reduced in adipose tissue from obese mice and humans. Our findings indicate that adipose tissue B_reg cells are a naturally occurring regulatory B cell subset that maintains homeostasis within adipose tissue and that B_reg cell dysfunction contributes pivotally to the progression of adipose tissue inflammation in obesity.