Aging induced changes in the microbiome affect the crosstalk and activity of monocytes and B1a cells

Abstract

Abstract Aging is thought to mostly dysregulate conventional B2 cells while leaving unaffected innate B1 cells. We recently questioned this assumption by providing evidence that upon aging, in humans, macaques and mice, B1a cells become converted into 4-1BBL+mTNFa+MHC class-IHiCD86Hi B cells (4BL cells) 1,2. Here we report that this conversion is induced by changes in the gut microbiota. Metabolites of the aging gut microbiota initiate monocyte infiltration in the omentum, where they convert B1a cells into 4BL cells. By utilizing 4-1BBL-41BB and mTNFa-TNFRII axes, 4BL cells further induce granzyme B (GrB)-expressing cytolytic CD8+T cells. Thus, for the first time, we provide a mechanistic proof that innate B1a cells also become dysregulated in aging of mammals, resulting in the loss of their immunosuppressive function and the gain of a new function – ability to induce potentially antitumor and autoimmune CD8+T cells. Our data shows the role of the microbiome/monocyte/B-cell/CD8-cell network in several aging-associated diseases. This work was supported by the Intramural Research Program, NIA/NIH, and CRADA with Janssen Research & Development, LLC, USA