The generation of memory B cells is maintained, but the antibody response is not, in the elderly after repeated influenza immunizations

Abstract

The success of a vaccine in inducing a protective antibody response depends on the longevity of both long-lived plasma cells (PC) and memory B cells. We have previously shown that the in vivo antibody response to a new influenza vaccine, the ex vivo plasmablast response, the in vitro B cell function, measured by AID (activation-induced cytidine deaminase), and the transcription factor E47, are significantly associated and decreased in elderly individuals. We hypothesized that because AID is decreased in the elderly, the ability to generate memory B cells would also be decreased, but our findings here show that memory B cells are maintained in the elderly probably due to further amplification in response to repeated vaccination. We recruited young and elderly individuals immunized in at least two consecutive influenza vaccine seasons in which the influenza A viral strains H1N1 and H3N2 in the vaccine were the same as in the previous year. PBMC were cultured with CpG/IL2 to measure the frequency of IgG vaccine-specific memory B cells. Serum antibody response was measured by hemagglutination inhibition assay. Blood plasmablasts were measured by flow cytometry. Surprisingly, the frequencies of influenza vaccine-specific memory B cells and plasmablasts were similar in young and elderly individuals, but the fold-increase in serum titers after vaccination was lower in the elderly although most of the elderly were seroprotected. We then measured the transcription factor Blimp-1, considered the master regulator of PC differentiation, and found it significantly reduced in cultures of B cells from elderly versus young individuals, as well as E47/AID and IgG secretion. Taken together, these results suggest an impaired memory B cell to PC differentiation in the elderly.

Paradoxical aging in HIV: immune senescence of B Cells is most prominent in young age

“…It has previously been shown in HIV children and recently confirmed in elderly HC that MBC are not affected by prior vaccination [8, 18, 39, 40]. To augment the immunologic assessment, cellular respon-ses of B cells following vaccination were also determined by ELISpot for memory B cells (MBC) on day 21 and for spontaneous antibody secreting cells (ASC) on day 7, and both assays revealed contrasting effects of age in HIV and HC.…”

Antibody Responses to Trivalent Inactivated Influenza Vaccine in Health Care Personnel Previously Vaccinated and Vaccinated for The First Time

“…It has to be mentioned that Group 1 has a higher average age than any of other groups. Reduced HI antibody response, lower frequency of vaccine-specific antibody-secreting cells, and decreased memory B cell to plasma cell differentiation have been described in elderly people aged 60 years or over when compared to young and middle-aged adults after receiving seasonal influenza vaccine354142. Nevertheless, the average age of Group 1 was 34.2 ± 9.2 years, seven subjects of Group 1 aged between 21 to 30 years, six aged between 31 to 40 years, four aged between 41 to 50 years and only one aged 57 years.…”

B Cell–Specific Biomarkers for Optimal Antibody Responses to Influenza Vaccination and Molecular Pathways That Reduce B Cell Function with Aging

“…This finding suggests that in this case low seroconversion in the elderly is mostly due to cell intrinsic defects in the differentiation of plasma cells. 57 One explanation for similar memory B cell responses in young and elderly individuals, despite lower AID in the elderly, is that IgG+ cells in the latter can be positively selected and can proliferate in response to repeated vaccines, as has been seen in mice. 58 Similar to our results, memory B cells but not antibody responses have been shown to be maintained in both immunodeficient HIV-infected children and in controls vaccinated yearly with the influenza vaccine.…”