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Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences

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  • Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences

    Biogerontology. 2019 May 2. doi: 10.1007/s10522-019-09811-8. [Epub ahead of print]
    Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences.

    Arsenović-Ranin N1, Petrović R2, Živković I2, Bufan B1, Stoiljković V3, Leposavić G4.
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    Abstract

    The study examined sex-specificities in age-related changes in BALB/c mice IgG antibody responses to immunisation with trivalent inactivated split-virus influenza bulk. Aging diminished the total serum IgG antibody responses to H1N1 and H3N2 and B influenza virus antigens in mice of both sexes, but they remained greater in aged females. This sex difference in aged mice correlated with the greater post-immunisation increase in the frequency of spleen germinal centre (GC) B cells and more favourable T follicular regulatory (Tfr)/GC B cell ratio, as Tfr cells are suggested to control antibody production through suppression of glycolysis. The greater post-immunisation GC B cell response in aged females compared with males correlated with the greater proliferation of B cells and CD4+ cells in splenocyte cultures from aged females restimulated with inactivated split-virus influenza from the bulk. To support the greater post-immunisation increase in the frequency GC B cell in aged females was more favourable Tfr/T follicular helper (Tfh) cell ratio. Additionally, compared with aged males, in age-matched females the greater avidity of serum IgG antibodies was found. However, in aged females IgG2a/IgG1 antibody ratio, reflecting spleen Th1/Th2 cytokine balance, was shifted towards IgG1 when compared with age-matched male mice. This shift was ascribed to a more prominent decline in the titres of functionally important IgG2a antibodies in females with aging. The study suggest that biological sex should be considered as a variable in designing strategies to manipulate with immune outcome of immunisation in aged animals, and possibly, at very long distance, humans.


    KEYWORDS:

    Aging; IgG antibody avidity; IgG2a/IgG1 ratio; Influenza vaccine; Sex differences; Tfr/Tfh cell ratio

    PMID: 31049769 DOI: 10.1007/s10522-019-09811-8
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