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

• Published in: The Journal of immunology (1950) Vol. 210; no. 1_Supplement; pp. 60 - 60.06
• Main Authors: Greer, Braxton D, Maul, Robert W, Gearhart, Patricia J
• Format: Journal Article
• Language: English
• Published: 01.05.2023
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.210.Supp.60.06

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