Document Detail


In senescence, age-associated B cells secrete TNFα and inhibit survival of B-cell precursors.
MedLine Citation:
PMID:  23410004     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Michelle Ratliff; Sarah Alter; Daniela Frasca; Bonnie B Blomberg; Richard L Riley
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Aging cell     Volume:  12     ISSN:  1474-9726     ISO Abbreviation:  Aging Cell     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-18     Completed Date:  2013-08-27     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  101130839     Medline TA:  Aging Cell     Country:  England    
Other Details:
Languages:  eng     Pagination:  303-11     Citation Subset:  IM    
Copyright Information:
© 2013 Blackwell Publishing Ltd/Anatomical Society.
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MeSH Terms
Descriptor/Qualifier:
Adoptive Transfer
Aging / metabolism*
Animals
Antigens, CD / metabolism
Apoptosis / drug effects
B-Lymphocyte Subsets / cytology,  metabolism*
Bone Marrow / metabolism
Cell Differentiation
Cell Survival / drug effects
Cells, Cultured
DNA-Binding Proteins / deficiency,  genetics
Immunophenotyping
Interleukin-10 / metabolism
Lymphocyte Activation
Lymphopoiesis*
Mice
Mice, Knockout
Precursor Cells, B-Lymphoid / cytology,  metabolism*
Spleen / cytology,  metabolism
Tumor Necrosis Factor-alpha / biosynthesis,  secretion*
Grant Support
ID/Acronym/Agency:
AG 023717/AG/NIA NIH HHS; AG 025256/AG/NIA NIH HHS; R01 AG025256/AG/NIA NIH HHS; R37 AG023717/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/DNA-Binding Proteins; 0/IL10 protein, mouse; 0/Rag2 protein, mouse; 0/Tumor Necrosis Factor-alpha; 130068-27-8/Interleukin-10
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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