title: Aging-dependent exclusion of antigen-inexperienced cells from the peripheral B cell repertoire.
abstract: Aging is accompanied by greatly reduced B cell production in the bone marrow, yet peripheral B cell numbers do not decline. We hypothesize that this may reflect filling of the peripheral pool with B cells that are long-lived as a consequence of specificity for, and chronic stimulation by, environmental Ags. To begin to explore this possibility, we analyzed the effects of aging on B cell population dynamics in the anti-H2(k/b) 3-83 mu-delta Ig-transgenic mouse. We predicted that, because they presumably do not bind environmental Ags, B cells bearing the transgenic receptor may be lost in aged animals. As seen in nontransgenic animals, total splenic B cell numbers remained constant with age in the Ig-transgenic animals despite reduced B cell production. Importantly, although the few newly produced B cells in the bone marrow of aged mice are 3-83 positive, the peripheral compartment of these mice is dominated by B cells that express endogenous Ig genes rather than the transgenes. This population includes large numbers of marginal zone-like and CD21(low/-)CD23(low/-)IgM(low) B cells, as well as elevated numbers of CD5+ B cells. Many of these cells express only non-B220 CD45 isoforms, suggesting that they may be memory cells. A significant proportion of aged transgenic animals produce autoantibodies that are reactive with ssDNA, dsDNA, or histones. Results support the hypothesis that, in the face of severely reduced production with age, B cells are selected based on reactivity to environmental Ags, accumulate, and display activated phenotypes. Cells bearing 3-83-transgenic receptors are excluded from this population due to their specificity. Beyond their importance in aging, these findings define a novel form of receptor revision in which B cells are selected rather than deleted based on Ag reactivity.
authors: Integrated Department of Immunology, University of Colorado Health Science Center and National Jewish Medical and Research Center, 1400 Jackson Street, RM K1004, Denver, CO 80206.
authors: Sara A
authors: SA
authors: Johnson
authors: Stephen J
authors: SJ
authors: Rozzo
authors: John C
authors: JC
authors: Cambier
mesh_terms: D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000941:Antigens / Q000096:biosynthesis*; D001323:Autoantibodies / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology*; D001402:B-Lymphocytes / Q000166:cytology / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D005260:Female; D005803:Genes, Immunoglobulin; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D007130:Immunoglobulin Idiotypes / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007138:Immunoglobulin delta-Chains / Q000096:biosynthesis / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis / Q000235:genetics; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D000941:Antigens; D001323:Autoantibodies; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D007138:Immunoglobulin delta-Chains; D007148:Immunoglobulin mu-Chains; D017493:Leukocyte Common Antigens