Compromised steady‐state germinal center activity with age in nonhuman primates

Abstract

Age-related reductions in vaccine-induced B cells in aging indicate that germinalcenters (GCs), the anatomical site where the development of humoral responses takes place, may lose efficacy with age. We have investigated the baseline follicular and GC composition in nonhuman primates (NHPs) with respect to their age. There was a marked reduction in follicular area in old animals. We found significantly lower normalized numbers of follicular PD1 hi CD4 T (Tfh) and proliferating (Ki67 hi ) GC B cells with aging, a profile associated with significantly higher numbers of potential follicular suppressor FoxP3 hi Lag3 hi CD4 T cells. Furthermore, a positive correlation was found between Tfh and follicular CD8 T cells (fCD8) only in young animals.Despite the increased levels of circulating preinflammatory factors in aging, young animals had higher numbers of monocytes and granulocytes in the follicles, a profile negatively associated with numbers of Tfh cells. Multiple regression analysis showed an altered association between GC B cells and other GC immune cell populations in old animals suggesting a differential mechanistic regulation of GC activity in aging.Our data demonstrate defective baseline GC composition in old NHPs and provide an immunological base for further understanding the adaptive humoral responses with respect to aging.

Aging and Options to Halt Declining Immunity to Virus Infections

“…Downregulation of AID and E47, caused by the pro-inflammatory microRNAs (miR-155 and miR-16), has been observed in B cells from aging individuals (241). Reduction in size and output of the germinal centers, as a consequence of a sub-optimal T cell help to B cells, have been reported upon infection and vaccination (79,133,(242)(243)(244). As demonstrated in older adults and aged mice, inflammation also leads to a decrease of chemokine CXCL12 production, which may impair the recruitment and accumulation of plasma cells in the bone marrow, the major site for antibody production (245,246).…”

The role of SARS‐CoV‐2 antibodies in COVID‐19: Healing in most, harm at times

“…Clues to the nature of such antibody characteristics might be provided by studies of dengue virus infection, where low antibody neutralization activity correlated with low avidity of antigen binding to antibody Fab regions 14 while ADE correlated with an altered glycosylation profile of the Fc region of IgG antibodies, which enhanced binding of antibodies to FcγRs on immune cells and the uptake of virus complexed with antibodies into those cells. 15 As both production of high avidity antibodies, which is dependent on germinal centre function, and antibody glycosylation are adversely affected by older age, 16,17 these characteristics of IgG antibody function might be age-related risk factors for COVID-19 (Fig. 1) and require investigation.…”

Potential of Mesenchymal Stem Cells in the Rejuvenation of the Aging Immune System

“…Sidler et al found alterations in the gene expression of cell cycle regulation of old rats, resulting in a large proportion of splenic and thymic cells with incomplete cell division [ 46 ]. The effect of senescent HSCs is also apparent in the early thymocyte progenitor (ETP) activity, in which T cell differentiation is reduced, apoptotic activity is heightened and Ki67+ cells are reduced [ 44 , 45 , 47 ]. Thymic involution is an inevitable process of aging but induced pluripotent stem cells (iPSCs) have shown promising results in the regeneration of thymic epithelium.…”