title: Chronic B cell deficiency from birth prevents age-related alterations in the B lineage.
abstract: Aging is accompanied by a decline in B lymphopoiesis in the bone marrow and accumulation of long-lived B cells in the periphery. The mechanisms underlying these changes are unclear. To explore whether aging in the B lineage is subjected to homeostatic regulation, we used mutant mice bearing chronic B cell deficiency from birth. We show that chronic B cell deficiency from birth, resulting from impaired maturation (CD19(-/-) and CD74(-/-)) or reduced survival (baff-r(-/-)), prevents age-related changes in the B lineage. Thus, frequencies of early and late hematopoietic stem cells, B lymphopoiesis, and the rate of B cell production do not substantially change with age in these mice, as opposed to wild-type mice where kinetic experiments indicate that the output from the bone marrow is impaired. Further, we found that long-lived B cells did not accumulate and peripheral repertoire was not altered with age in these mice. Collectively, our results suggest that aging in the B lineage is not autonomously progressing but subjected to homeostatic regulation.
authors.affiliation: Department of Immunology, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel.
authors.forename: Zohar
authors.initials: Z
authors.lastname: Keren
authors.forename: Dana
authors.initials: D
authors.lastname: Averbuch
authors.forename: Gitit
authors.initials: G
authors.lastname: Shahaf
authors.forename: Simona
authors.initials: S
authors.lastname: Zisman-Rozen
authors.forename: Karin
authors.initials: K
authors.lastname: Golan
authors.forename: Tomer
authors.initials: T
authors.lastname: Itkin
authors.forename: Tsvee
authors.initials: T
authors.lastname: Lapidot
authors.forename: Ramit
authors.initials: R
authors.lastname: Mehr
authors.forename: Doron
authors.initials: D
authors.lastname: Melamed
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D053265:B-Cell Activation Factor Receptor / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage; D002469:Cell Separation; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006706:Homeostasis / Q000276:immunology*; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology
chemical_list: D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D053265:B-Cell Activation Factor Receptor; D000949:Histocompatibility Antigens Class II; D011947:Receptors, Antigen, B-Cell; C045084:invariant chain