B cell dysfunction during aging is not dependent on stem cell aging

Abstract Humoral immune responses to vaccination are a critical component of protection from infectious diseases. Older humans simultaneously have reduced antibody production in response and an increased burden mortality when infected with viral respiratory infections such as influenza or SARS-CoV-2. Therefore, it is understand molecular drivers immunosenescence order develop strategies that better protect the elderly. By adoptively transferring naïve B cells old young mice into cell-depleted recipients, our lab has characterized germinal center dynamics model antigen, nitrophenyl-chicken gamma globulin (NP-CGG). were found be antigen specific produced anti-NP antibodies. failed produce antibodies had large proportion non-specific cells. We sought uncover origin this age-related deficiency. hypothesized age-induced changes hematopoietic stem (HSCs) might passed on mature disrupt their function. transplanted HSCs donors young, irradiated recipients analyzed ability progeny mount response. To surprise, HSC age did not encode cell function, both donor ages could NP-specific response, implicating alternative source aging dysfunction. Further study cause dysfunction will guide development vaccine additives improve protective immunity Supported by NIA intramural funding.