title: Lasting antibody responses are mediated by a combination of newly formed and established bone marrow plasma cells drawn from clonally distinct precursors.
abstract: Current models hold that serum Ab titers are maintained chiefly by long-lived bone marrow (BM) plasma cells (PCs). In this study, we characterize the role of subpopulations of BM PCs in long-term humoral responses to T cell-dependent Ag. Surprisingly, our results indicate that 40-50% of BM PCs are recently formed cells, defined, in part, by rapid steady-state turnover kinetics and secretion of low-affinity IgM Abs. Further, for months after immunization with a hapten-protein conjugate, newly formed Ag-induced, IgM-secreting BM PCs were detected in parallel with longer-lived IgG-secreting cells, suggesting ongoing and parallel input to the BM PC pool from two distinct pools of activated B cells. Consistent with this interpretation, IgM and IgG Abs secreted by cells within distinct PC subsets exhibited distinct L chain usage. We conclude that long-term Ab responses are maintained by a dynamic BM PC pool composed of both recently formed and long-lived PCs drawn from clonally disparate precursors.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;
authors.forename: Irene
authors.initials: I
authors.lastname: Chernova
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;
authors.forename: Derek D
authors.initials: DD
authors.lastname: Jones
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;
authors.forename: Joel R
authors.initials: JR
authors.lastname: Wilmore
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bortnick
authors.affiliation: Department of Bioengineering, Ege University, 35100, Izmir, Turkey; and.
authors.forename: Mesut
authors.initials: M
authors.lastname: Yucel
authors.affiliation: School of Biomedical Engineering Science and Health Systems, Drexel University, Philadelphia, PA 19104.
authors.forename: Uri
authors.initials: U
authors.lastname: Hershberg
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; dallman@mail.med.upenn.edu.
authors.forename: David
authors.initials: D
authors.lastname: Allman
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism; D019070:Cell Lineage / Q000276:immunology; D005260:Female; D056724:Immunity, Humoral; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis*; D007156:Immunologic Memory; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D007075:Immunoglobulin M; D007073:Immunoglobulin E