Abstract
Memory B (B(MEM)) cells and long-lived bone marrow plasma cells (BM-PCs) persist within local environmental survival niches that afford cellular longevity. However, the factors supporting B(MEM) cell survival within the secondary lymphoid organs and allowing BM-PC persistence in the bone marrow remain poorly characterized. We report herein that long-lived B(MEM) cell survival and function are completely independent of BAFF (B cell-activating factor of the TNF family) or APRIL (a proliferation-inducing ligand). Thus, B(MEM) cells represent the only mature B2 lineage subset whose survival is independent of these ligands. We have previously shown that the TNFR family member receptor BCMA (B cell maturation Ag) is a critical survival receptor for BM-PC survival in vivo. We identify in this study the ligands critical for BM-PC survival and show that either BAFF or APRIL supports the survival of BM-PCs in vivo. These data define the BAFF/APRIL-dependent and -independent components of long-lived humoral immunity.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antibody Formation / genetics
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B-Cell Activating Factor / metabolism
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B-Cell Activating Factor / physiology*
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B-Cell Activation Factor Receptor / biosynthesis
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B-Cell Activation Factor Receptor / genetics
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B-Cell Activation Factor Receptor / metabolism
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B-Cell Maturation Antigen / biosynthesis
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B-Cell Maturation Antigen / genetics
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B-Cell Maturation Antigen / metabolism
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B-Lymphocyte Subsets / cytology
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B-Lymphocyte Subsets / immunology*
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B-Lymphocyte Subsets / metabolism
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Bone Marrow Cells / cytology
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Bone Marrow Cells / immunology
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Bone Marrow Cells / metabolism
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Cell Survival / genetics
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Cell Survival / immunology
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Immunologic Memory* / genetics
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Plasma Cells / cytology
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Plasma Cells / immunology
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Plasma Cells / metabolism
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Transmembrane Activator and CAML Interactor Protein / biosynthesis
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Transmembrane Activator and CAML Interactor Protein / genetics
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Tumor Necrosis Factor Ligand Superfamily Member 13 / deficiency
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Tumor Necrosis Factor Ligand Superfamily Member 13 / genetics
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Tumor Necrosis Factor Ligand Superfamily Member 13 / physiology*
Substances
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B-Cell Activating Factor
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B-Cell Activation Factor Receptor
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B-Cell Maturation Antigen
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Tnfrsf13b protein, mouse
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Tnfsf13 protein, mouse
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Tnfsf13b protein, mouse
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Transmembrane Activator and CAML Interactor Protein
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Tumor Necrosis Factor Ligand Superfamily Member 13