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

Kimberly Shankwitz, Suresh Pallikkuth, Tirupataiah Sirupangi, Daniel Kirk Kvistad, Kyle Blaine Russel, Rajendra Pahwa, Lucio Gama, Richard A. Koup, Li Pan, Francois Villinger, Savita Pahwa, Constantinos Petrovas

Research output: Contribution to journalArticle

Abstract

Age-related reductions in vaccine-induced B cells in aging indicate that germinal centers (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 PD1hi CD4 T (Tfh) and proliferating (Ki67hi) GC B cells with aging, a profile associated with significantly higher numbers of potential follicular suppressor FoxP3hiLag3hi 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.

Original languageEnglish (US)
Article numbere13087
JournalAging Cell
DOIs
StateAccepted/In press - Jan 1 2019

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Keywords

  • aging
  • B cells
  • follicles
  • Tfh cells

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Shankwitz, K., Pallikkuth, S., Sirupangi, T., Kirk Kvistad, D., Russel, K. B., Pahwa, R., Gama, L., Koup, R. A., Pan, L., Villinger, F., Pahwa, S., & Petrovas, C. (Accepted/In press). Compromised steady-state germinal center activity with age in nonhuman primates. Aging Cell, [e13087]. https://doi.org/10.1111/acel.13087