Intrinsic defects in B cell response to seasonal influenza vaccination in elderly humans

Abstract

We have evaluated the serum response to seasonal influenza vaccination in subjects of different ages and associated this with the specific B cell response to the vaccine in vitro. Although the serum response has previously been shown to decrease with age, this has largely been associated to decreased T cell functions. Our results show that in response to the vaccine, the specific response of B cells in vitro, as measured by AID (activation-induced cytidine deaminase), the in vivo serum HI (hemagglutination inhibition) response, and the in vivo generation of switch memory B cells are decreased with age, as evaluated in the same subjects. This is the first report to demonstrate that intrinsic B cell defects with age contribute to reduced antibody responses to the influenza vaccine. The level of AID in response to CpG before vaccination can also predict the robustness of the vaccine response. These results could contribute to developing more effective vaccines to protect the elderly as well as identifying those most at risk.

Vaccination against pandemic H1N1 (2009) in patients after allogeneic hematopoietic stem cell transplantation: a retrospective analysis

“…The central role of B cells in the vaccination response has already been shown by Frasca et al, who demonstrated that intrinsic B cell defects in the elderly contribute to reduced antibody responses to influenza vaccine [32].…”

A novel B cell population revealed by a CD38/CD24 gating strategy: CD38−CD24− B cells in centenarian offspring and elderly people

“…Moreover, the inability of old individuals to effectively respond to vaccines results in less effective immunizations against viruses and bacteria, thus increasing the risk of infections and diseases (Miller and Cancro 2007;Cancro et al 2009;Gibson et al 2009;Dunn-Walters and Ademokun 2010;Frasca and Blomberg 2011). Indeed, it is well documented that the immune response to vaccination declines with age, although the reasons for this are poorly understood (Kumar and Burns 2008;Frasca et al 2010;McElhaney et al 2012). It is also known that in the elderly, there is an impairment of both innate and adaptive immune responses.…”

“…It has been widely reported that elderly people show changes in B cell number, low levels of antibody production, and poor responses to recall antigens, and a collapse in B cell receptor repertoire diversity correlated with poor health status and the impairment of antibody response (Miller and Cancro 2007;Kumar and Burns 2008;Cancro et al 2009;Gibson et al 2009;DunnWalters and Ademokun 2010;Frasca et al 2010;Frasca and Blomberg 2011;McElhaney et al 2012). Lower numbers and percentages of B cells also form part of the cluster of immune parameters collectively known as the "Immune Risk Profile" associated with 2-, 4-, and 6-year mortality of the very elderly in the Swedish OCTO/ NONA longitudinal studies (Pawelec et al 2005).…”

B cells and immunosenescence: A focus on IgG+IgD−CD27− (DN) B cells in aged humans

“…However, in vitro stimulation of human peripheral blood B cells by anti-CD40 and IL-4 induces a lower production of IgG from elderly donors, correlated to a reduction of the transcription factor E47 and AID in old people (Frasca et al, 2008). Moreover the same authors have recently demonstrated that the level of AID in response to polyclonal stimulation by CpG can predict the size of the response to influenza vaccination (Frasca et al, 2010a).…”