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

• Published in: Biogerontology (Dordrecht) 2019-08, Vol.20 (4), p.475-496
• Main Authors: Arsenović-Ranin, Nevena, Petrović, Raisa, Živković, Irena, Bufan, Biljana, Stoiljković, Vera, Leposavić, Gordana
• Format: Article
• Language: English
• Subjects: Age Factors; Aging; Aging - immunology; Animals; Antibody Formation - physiology; Antibody response; Antigens; Avidity; Biomedical and Life Sciences; CD4 antigen; Cell Biology; Cell proliferation; Developmental Biology; Female; Females; Geriatrics/Gerontology; Germinal Center - immunology; Germinal centers; Glycolysis; Humans; Immunity, Active - physiology; Immunization; Immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin G - classification; Influenza; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H3N2 Subtype - immunology; Life Sciences; Lymphocytes B; Lymphocytes T; Male; Males; Mice; Mice, Inbred BALB C; Research Article; Sex; Sex Factors; Spleen
• ISSN: 1389-5729; 1573-6768
• DOI: 10.1007/s10522-019-09811-8

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.