High TNF-alpha levels in resting B cells negatively correlate with their response

摘要

Aging significantly decreases the influenza vaccine-specific response as we and others have previously shown. Based on our previous data in aged mice, we hypothesize that the inflammatory status of the individual and of B cells themselves would impact B cell function. We here show that the ability to generate a vaccine-specific antibody response is negatively correlated with levels of serum TNF-alpha. Moreover, human unstimulated B cells from elderly make higher levels of TNF-alpha than those from young individuals, and these positively correlate with serum TNF-alpha levels. These all negatively correlate with B cell function, measured by activation-induced cytidine deaminase, the enzyme of class switch recombination and somatic hypermutation. Only memory B cells (either IgM or switched), but not naive B cells, make appreciable levels of TNF-alpha and more in elderly as compared to young individuals. Finally, an anti-TNF-alpha antibody can increase the response in cultured B cells from the elderly, suggesting that TNF-alpha secreted by memory B cells affects IgM memory B cells and naive B cells in an autocrine and/or paracrine manner. Our results show an additional mechanism for reduced B cell function in the elderly and propose B cell-derived TNF-a as another predictive biomarker of in vivo and in vitro B cell responses.