B lymphocytes in human subcutaneous adipose crown-like structures

Accumulation of macrophages and T cells within crown-like structures (CLS) in subcutaneous adipose tissue predicts disease severity in obesity related insulin resisance (OIR). While rodent data suggest the B cell is an important feature of these lesions, B cells have not been described within the human CLS. In order to identify B cells in the human subcutaneous CLS (sCLS) in obese subjects and determine if the presence of B cells predict insulin resistance, we examined archived samples of subcutaneous and omental fat from 32 obese men and women and related findings to clinical parameters. Using immunohistochemistry we identified B (CD19+) and T cells (CD3+) within the sCLS and perivascular space. B cell presence and density (B cells pHPF, T cells pHPF and B:T cell ratio) were compared with measures of insulin resistance (HOMA) and other variables. In sixteen of thirty-two subjects (50%) CD19+ B cells were localized within sCLS and were relatively more numerous than T cells. HOMA was not different between subjects with CD19+ vs. CD19− sCLS (5.5 vs. 5.3, p= 0.88). After controlling for diabetes and glycemia (HA1c), the B:T cell ratio correlated with current metformin treatment (r=0.89, p = 0.001). These results indicate that in human OIR, B cells are an integral component of organized inflammation in subcutaneous fat, and defining their role will lead to a better understanding of OIR pathogenesis and potentially impact treatment.