CONSEQUENCE OF AGE-INDUCED SHIFT IN B CELL SUBSETS With age the generation of naive helper T cells and follicular B cells, that are both needed for the generation of high affinity antibody (Ab), become compromised and current vaccines for the elderly that depend on inducing these, become ineffective. Thus the elderly, though protected by Ab already in place for pathogens encountered earlier in life, are highly susceptible to new strains of virus and newly emerged pathogens. We noted the generation of an unusual population of antibody-secreting B cells to live influenza infection in aged mice, that is derived by stimulation of recently described age-associated B cells (ABC). These induced ABC (iABC) are generated independently of CD4 T cell help, but seem to depend on stimulation by pathogen- associated danger signals. Live Influenza infection induces substantial iABC making influenza-specific Ab indicating this pathway may contribute significantly to protective immunity to influenza. If so it is important to define how ABC develop, and what signals optimally drive them to become iABC -producing Ab and possible some kind of long-lived memory. Here we will determine if the ABC response can indeed be harnessed to provide protective Ab responses against influenza in aged mice. Have developed transfer approaches that allow us to evaluate whether ABC or the Ab produced by ABC in response to by influenza A virus can provide protection against lethal virus, and can effective neutralize or otherwise clear infection with influenza especially in the contest of the elderly host. If we find the aged ABC make a strong contribution to immunity in otherwise compromised aged hosts, it will justify a major effort to define the pathways that effectively induce ABC response so they can be harnessed in future to improve vaccines and therapies for the aged.

Public Health Relevance

Current vaccines offer the elderly little protection against influenza, leaving them vulnerable to yearly strains and to a potentially catastrophic new pandemic. This failure stems from loss of T cell helper response and the B cell responses they drive, that are both compromised by age. We find influenza infection also induces an age-associated B cell population (ABC) to make antibody to influenza. This requires pathogen 'danger signals' but not T cell help, and we will ask if this response can be harnessed to augment immunity in the elderly.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Exploratory/Developmental Grants (R21)
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Immunity and Host Defense (IHD)
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Prabhudas, Mercy R
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University of Massachusetts Medical School Worcester
Schools of Medicine
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Swain, Susan L; Kugler-Umana, Olivia; Kuang, Yi et al. (2017) The properties of the unique age-associated B cell subset reveal a shift in strategy of immune response with age. Cell Immunol 321:52-60