Aging converts innate B1a cells into potent CD8+ T cell inducers

Catalina Lee-Chang, Monica Bodogai, Kanako Moritoh, Xin Chen, Robert Wersto, Ranjan Sen, Howard A. Young, Michael Croft, Luigi Ferrucci, Arya Biragyn

Research output: Contribution to journalArticle

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-IHi CD86Hi 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-gR1 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.

Original languageEnglish (US)
Pages (from-to)3385-3397
Number of pages13
JournalJournal of Immunology
Volume196
Issue number8
DOIs
StatePublished - Apr 15 2016
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Lee-Chang, C., Bodogai, M., Moritoh, K., Chen, X., Wersto, R., Sen, R., Young, H. A., Croft, M., Ferrucci, L., & Biragyn, A. (2016). Aging converts innate B1a cells into potent CD8+ T cell inducers. Journal of Immunology, 196(8), 3385-3397. https://doi.org/10.4049/jimmunol.1502034