Mechanisms for regulation of the human antibody response to the influenza vaccine and changes with age (176.19)

• Published in: The Journal of immunology (1950) Vol. 188; no. 1_Supplement; pp. 176 - 176.19
• Main Authors: Blomberg, Bonnie, Romero, Maria, Diaz, Alain, Mendez, Nicholas, Landin, Ana Marie, Frasca, Daniela
• Format: Journal Article
• Language: English
• Published: 01.05.2012
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.188.Supp.176.19

Aging is associated with a decline in the ability of the individual to mount protective immune responses, e.g. antibodies (immunoglobulins, Ig). Understanding the molecular mechanisms of the age-related impairment in immune functions will help to prevent infectious diseases and improve the biological quality of life in the elderly. We hypothesize that the increased pro-inflammatory status of the elderly, called inflammaging, impairs the capacity of the individual to make protective antibodies and to respond to vaccination. Our data indicate that aged B lymphocytes make TNF-α before vaccine challenge, which impairs their function,including optimal AID and class switch recombination (CSR) of Ig. We previously showed that the transcription factor E47 and enzyme, AID (activation-induced cytidine deaminase), both crucial for class switch recombination, are decreased with age in both mice and humans. We here report that human unstimulated (ex vivo) B cells from elderly have significantly higher levels of TNF-α than young subjects and that the t0 TNF level negatively correlates with the in vitro t28 influenza vaccine response (as measured by AID) which in turn correlates with the in vivo serum HAI response. Thus, these results reveal new molecular mechanisms which contribute to reduced antibody responses in aging and should have immediate impact on crucial development of effective vaccines to protect elderly individuals from diseases typical of old age.