• Open Access

In senescence, age-associated B cells secrete TNFα and inhibit survival of B-cell precursors

Authors


  • Supported by NIH grants AG 025256 to RLR and AG 023717 to BBB.

Correspondence

Richard L. Riley, Ph.D., Department of Microbiology & Immunology, University of Miami Miller School of Medicine, P.O. Box 016960 (R-138), Miami, FL 33101, USA. Tel.: +1-305-243-4779; fax: +1-305-243-4780; e-mail: rriley@med.miami.edu

Summary

Aged mice exhibit ~ 5–10-fold increases in an ordinarily minor CD21/35 CD23 mature B-cell subset termed age-associated B cells (ABCs). ABCs from old, but not young, mice induce apoptosis in pro-B cells directly through secretion of TNFα. In addition, aged ABCs, 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 that 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’ that promotes down-regulation of B lymphopoiesis in old age.

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