Reduced Ig class switch in aged mice correlates with decreased E47 and activation-induced cytidine deaminase

J Immunol. 2004 Feb 15;172(4):2155-62. doi: 10.4049/jimmunol.172.4.2155.

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

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AICDA (Activation-Induced Cytidine Deaminase)
  • Aging / immunology*
  • Aging / metabolism*
  • Animals
  • B-Lymphocyte Subsets / enzymology
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / metabolism
  • CD40 Antigens / pharmacology
  • Cells, Cultured
  • Cellular Senescence / immunology
  • Cytidine Deaminase / antagonists & inhibitors
  • Cytidine Deaminase / biosynthesis*
  • DNA / antagonists & inhibitors
  • DNA / metabolism
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation / immunology*
  • Enzyme Induction / immunology
  • Female
  • Heterozygote
  • Immunoglobulin Class Switching / genetics
  • Immunoglobulin Class Switching / physiology*
  • Immunoglobulin E / metabolism
  • Immunoglobulin G / metabolism
  • Interleukin-4 / pharmacology
  • Lymphocyte Activation / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Protein Binding / immunology
  • Recombination, Genetic / immunology
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • TCF Transcription Factors
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / biosynthesis
  • Transcription Factors / metabolism*
  • Transcription, Genetic / immunology

Substances

  • CD40 Antigens
  • DNA-Binding Proteins
  • Immunoglobulin G
  • TCF Transcription Factors
  • Tcf7l1 protein, mouse
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors
  • Interleukin-4
  • Immunoglobulin E
  • DNA
  • AICDA (Activation-Induced Cytidine Deaminase)
  • Cytidine Deaminase