Abstract
The capacity to class switch the IgH chain is critical to the effectiveness of humoral immune responses. We show that in vitro-stimulated splenic B cells from senescent mice are deficient in production of multiple class switch isotypes (IgG1, G2a, G3, and E), class switch recombination (CSR), and induction of the E2A-encoded transcription factor E47. E47 has previously been shown to be required for CSR, at least in part via expression of the activation-induced cytidine deaminase. Our studies show that impaired induction of E47, and subsequently activation-induced cytidine deaminase, contribute to poor CSR and production of secondary isotypes in senescence.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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AICDA (Activation-Induced Cytidine Deaminase)
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Aging / immunology*
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Aging / metabolism*
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Animals
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B-Lymphocyte Subsets / enzymology
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B-Lymphocyte Subsets / immunology
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B-Lymphocyte Subsets / metabolism
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CD40 Antigens / pharmacology
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Cells, Cultured
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Cellular Senescence / immunology
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Cytidine Deaminase / antagonists & inhibitors
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Cytidine Deaminase / biosynthesis*
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DNA / antagonists & inhibitors
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DNA / metabolism
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / metabolism*
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Down-Regulation / immunology*
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Enzyme Induction / immunology
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Female
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Heterozygote
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Immunoglobulin Class Switching / genetics
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Immunoglobulin Class Switching / physiology*
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Immunoglobulin E / metabolism
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Immunoglobulin G / metabolism
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Interleukin-4 / pharmacology
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Lymphocyte Activation / immunology*
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Protein Binding / immunology
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Recombination, Genetic / immunology
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Spleen / cytology
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Spleen / immunology
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Spleen / metabolism
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TCF Transcription Factors
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Transcription Factor 7-Like 1 Protein
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / biosynthesis
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Transcription Factors / metabolism*
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Transcription, Genetic / immunology
Substances
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CD40 Antigens
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DNA-Binding Proteins
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Immunoglobulin G
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TCF Transcription Factors
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Tcf7l1 protein, mouse
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Transcription Factor 7-Like 1 Protein
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Transcription Factors
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Interleukin-4
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Immunoglobulin E
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DNA
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AICDA (Activation-Induced Cytidine Deaminase)
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Cytidine Deaminase