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

Aging Cell

Michelle Ratliff¹  Sarah Alter¹  Daniela Frasca¹  Bonnie B. Blomberg¹ 

[1] Department of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL, USA

关键词: aging;    B cells;    B lymphopoeisis;    inflammation;    TNF alpha;    senescence;   

DOI  :  10.1111/acel.12055

来源: Wiley

【 摘 要 】

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.

【 授权许可】

Unknown   
© 2013 Blackwell Publishing Ltd/Anatomical Society