Abstract

Abstract Deficits in immune responses in the elderly contribute to their mortality and morbidity. In order to develop predictive markers for a beneficial humoral immune response, we evaluated the in vivo and in vitro response to the seasonal influenza vaccine in young and elderly individuals. We measured serum antibody response and associated this with the in vitro B cell response to the vaccine, measured by AID (activation-induced cytidine deaminase). AID is a measure of immunoglobulin class switch recombination, the process that generates protective antibodies, and is a good measure of B cell function. Both responses decrease with age and are significantly correlated. We hypothesize that the increased pro-inflammatory status of the elderly, called inflammaging, directly impacts B cell function, thus impairing the capacity of the individual to make protective antibodies and to respond to vaccination. Our data indicate that aged B lymphocytes themselves make TNF-α before vaccine challenge and this correlates with their impaired function, including reduced AID expression after B cell stimulation. Our results reveal new molecular mechanisms which contribute to reduced antibody responses in aging and suggest that these will have an impact for crucial development of effective vaccines to protect the elderly from infectious and other debilitating diseases.

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