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J Immunol. 2016 Apr 15;196(8):3385-97. doi: 10.4049/jimmunol.1502034. Epub 2016 Mar 16.

Aging Converts Innate B1a Cells into Potent CD8+ T Cell Inducers.

Author information

1
Immunoregulation Section, National Institute on Aging, Baltimore, MD 21224; INSERM UMR995, Lille Inflammation Research International Center, F-59000 Lille, France; University of Lille, F-59000 Lille, France;
2
Immunoregulation Section, National Institute on Aging, Baltimore, MD 21224;
3
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region, People's Republic of China; Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702;
4
Flow Cytometry Unit, National Institute on Aging, Baltimore, MD 21244;
5
Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD 21224;
6
Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702;
7
Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; and.
8
Translational Gerontology Branch, National Institute on Aging, Baltimore, MD 21224.
9
Immunoregulation Section, National Institute on Aging, Baltimore, MD 21224; biragyna@mail.nih.gov.

Abstract

B cell dysregulation in aging is thought to mostly occur in conventional B2 cells without affecting innate B1 cells. Elderly humans and mice also accumulate 4-1BBL(+)MHC class-I(Hi)CD86(Hi)B cells of unknown origin. In this article, we report that these cells, termed 4BL cells, are activated murine and possibly human B1a cells. The activation is mediated by aging human monocytes and murine peritoneal macrophages. They induce expression and activation of 4-1BBL and IFN-γR1 on B1a cells to subsequently upregulate membrane TNF-α and CD86. As a result, activated B1a/4BL cells induce expression of granzyme B in CD8(+)T cells by targeting TNFR2 via membrane TNF-α and providing costimulation with CD86. Thus, for the first time, to our knowledge, these results indicate that aging affects the function of B1a cells. Upon aging, these cells lose their tumor-supporting activity and become inducers of potentially antitumor and autoimmune CD8(+)T cells.

PMID:
26983789
PMCID:
PMC4821757
DOI:
10.4049/jimmunol.1502034
[Indexed for MEDLINE]
Free PMC Article

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