title: In senescence, age-associated B cells secrete TNFα and inhibit survival of B-cell precursors.
abstract: 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: Department of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors: Michelle
authors: M
authors: Ratliff
authors: Sarah
authors: S
authors: Alter
authors: Daniela
authors: D
authors: Frasca
authors: Bonnie B
authors: BB
authors: Blomberg
authors: Richard L
authors: RL
authors: Riley
mesh_terms: D019264:Adoptive Transfer; D000375:Aging / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation; D038041:Lymphopoiesis; D051379:Mice; D018345:Mice, Knockout; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D004268:DNA-Binding Proteins; C556062:IL10 protein, mouse; C499308:Rag2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10