Abstract
Obesity is a rapidly growing public health crisis associated simultaneously with increased metabolic disease and humoral immune suppression to vaccination or infection. Inflammatory CD11c+T-bet+ B cells increase in spleen and adipose tissue during obesity and exacerbate metabolic dysfunction via antibodies. We now find that during obesity Tbet+ B cells also expand in the liver but not omentum or mesenteric fat. Obese mice also develop increased splenic CXCR5+ T(FH) and hepatic CXCR5- T(PH) cells which serve as likely partners for antigen-experienced MHC-II+ CD11c+ Tbet+ B cells. We also observed that antibodies in obese mice, previously found to contribute to metabolic disease, largely circulate as inflammatory autoantigen-bound immune complexes. Obese mice lacking T-bet in B cells also develop increased autoantibody titers and expanded splenic germinal center (GC) B and T helper cells. T-bet+ B cell-deficient mice make a similarly enhanced GC, T(FH), T(PH) response to haptenated-protein vaccination with a corresponding increase in antibody affinity, although there is no additive effect of obesity. These results are consistent with GC inhibition by expanded CD11c+ B cells demonstrated by others to occur during autoimmunity, suggesting a broadly universal mechanism which may explain reduced humoral immunity and poor clinical outcomes following infection in patients with obesity and other forms of chronic inflammation.