Human B cell response to the influenza vaccine is predicted by AID and decreased by inflammaging
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1
Universtiy of Miami Miller School of Medicine, Microbiology and Immunology, United States
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 (CSR), the process that generates protective antibodies and memory B cells, and is a good measure of B cell function. Both responses decrease with age, are significantly correlated, and measures of AID in activated (mitogen) B cells at t0 (before vaccination) predict ability to respond to the vaccine. We hypothesized 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.
Acknowledgements
Work supported by NIH grants AG032576 (BBB) and AI096446-01A1 (BBB+DF).
References
1. Frasca D, Diaz A, Romero M, Landin AM, Phillips M, Lechner SC, Ryan JG, Blomberg BB. (2010) Intrinsic defects in B cell response to seasonal influenza vaccination in elderly humans. Vaccine, 28: 8077-8084
2. Frasca D, Diaz A, Romero M, Phillips M, Mendez N, Landin AM, Blomberg BB. (2012). Unique biomarkers for B cell function predict the serum response to pandemic H1N1 influenza vaccine. Int. Immunol. Int. Immunol., 24: 175-184.
3. Surender, K, Frasca, D, Blomberg, B, and Golding, H. (2012) AID activity in B cells strongly correlates with polyclonal antibody affinity maturation in-vivo following pandemic 2009-H1N1 vaccination in humans. PLoS Pathogen, Sep;8 (9): Epub 2012 Sep 13.
Keywords:
human,
Aging,
vaccine response,
B lymphocytes,
Antibodies,
biomarkers,
activation-induced cytidine deaminase (AID),
Inflammation
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Blomberg
BB,
Diaz
A,
Romero
M,
Landin
AM and
Frasca
D
(2013). Human B cell response to the influenza vaccine is predicted by AID and decreased by inflammaging.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00713
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Received:
13 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Bonnie B Blomberg, Universtiy of Miami Miller School of Medicine, Microbiology and Immunology, Miami, FL, 33136, United States, bblomber@med.miami.edu