High TNF-α levels in resting B cells negatively correlate with their response.
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-α. Moreover, human unstimulated B cells from elderly make higher levels of TNF-α than those from young individuals, and these positively correlate with serum TNF-α 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 naïve B cells, make appreciable levels of TNF-α and more in elderly as compared to young individuals. Finally, an anti-TNF-α antibody can increase the response in cultured B cells from the elderly, suggesting that TNF-α secreted by memory B cells affects IgM memory B cells and naïve 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-α as another predictive biomarker of in vivo and in vitro B cell responses.
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA. Electronic address: dfrasca@med.miami.edu.
Daniela
D
Frasca
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA; School of Advanced Studies, Doctorate in Medical-Surgical, Clinical and Experimental Sciences, University G.d'Annunzio, Chieti, 66013, Italy.
Alain
A
Diaz
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA.
Maria
M
Romero
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA.
Ana Marie
AM
Landin
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA.
Bonnie B
BB
Blomberg
D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D055815:Young Adult
D007252:Influenza Vaccines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha
Aging; B cells; Inflammation; Vaccine responses