In Senescence, Age-associated B Cells (ABC) Secrete TNFα and Inhibit Survival of B Cell Precursors.

Department of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL, 33136.
Aging cell (Impact Factor: 7.55). 02/2013; DOI: 10.1111/acel.12055
Source: PubMed

ABSTRACT Aged mice exhibit ~ 5-10 fold increases in an ordinarily minor CD21/35(-) CD23(-) mature B cell subset termed age-associated B cells (ABC). ABC from old, but not young, mice induce apoptosis in pro-B cells directly through secretion of TNFα. In addition, aged ABC, via TNFα, stimulate bone marrow cells to suppress pro-B cell growth. ABC effects can be prevented by the anti-inflammatory cytokine IL-10. Notably, CD21/35(+) CD23(+) follicular (FO) splenic and FO-like recirculating bone marrow B cells in both young and aged mice contain a subpopulation which produces IL-10. Unlike young adult FO B cells, old FO B cells also produce TNFα; however, secretion of IL-10 within this B cell population ameliorates the TNFα-mediated effects on B cell precursors. Loss of B cell precursors in the bone marrow of old mice in vivo was significantly associated with increased ABC relative to recirculating FO-like B cells. Adoptive transfer of aged ABC into RAG-2 KO recipients resulted in significant losses of pro-B cells within the bone marrow. These results suggest that alterations in B cell composition during old age, in particular the increase in ABC within the B cell compartments contribute to a pro-inflammatory environment within the bone marrow. This provides a mechanism of inappropriate B cell "feedback" which promotes down-regulation of B lymphopoiesis in old age. © 2013 Blackwell Publishing Ltd/Anatomical Society.

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