Supported by NIH grants AG 025256 to RLR and AG 023717 to BBB.
In senescence, age-associated B cells secrete TNFα and inhibit survival of B-cell precursors*
Article first published online: 17 MAR 2013
© 2013 Blackwell Publishing Ltd/Anatomical Society
Volume 12, Issue 2, pages 303–311, April 2013
How to Cite
Ratliff, M., Alter, S., Frasca, D., Blomberg, B. B. and Riley, R. L. (2013), In senescence, age-associated B cells secrete TNFα and inhibit survival of B-cell precursors. Aging Cell, 12: 303–311. doi: 10.1111/acel.12055
- Issue published online: 17 MAR 2013
- Article first published online: 17 MAR 2013
- Accepted manuscript online: 15 FEB 2013 04:35AM EST
- Manuscript Accepted: 5 FEB 2013
- B cells;
- B lymphopoeisis;
- TNF alpha;
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.