In senescence, age-associated b cells secrete tnfα and inhibit survival of b-cell precursors

Michelle Ratliff, Sarah Alter, Daniela Frasca, Bonnie B. Blomberg, Richard L. Riley

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


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 TNF, stimulate bone marrow cells to suppress pro-Bcell 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 downregulation of B lymphopoiesis in old age.

Original languageEnglish (US)
Pages (from-to)303-311
Number of pages9
JournalAging Cell
Issue number2
StatePublished - 2013


  • Aging
  • B cells
  • B lymphopoeisis
  • Inflammation
  • Senescence.
  • TNF alpha

ASJC Scopus subject areas

  • Cell Biology
  • Aging


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