Reduced Ig class switch in aged mice correlates with decreased E47 and activation-induced cytidine deaminase.
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.
Frasca
Daniela
D
Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL 33136, USA.
Van der Put
Elaine
E
Riley
Richard L
RL
Blomberg
Bonnie B
BB
D000375:Aging / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000494:pharmacology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000276:immunology; D003564:Cytidine Deaminase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004247:DNA / Q000037:antagonists & inhibitors / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D015536:Down-Regulation / Q000276:immunology*; D004790:Enzyme Induction / Q000276:immunology; D005260:Female; D006579:Heterozygote; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000502:physiology*; D007073:Immunoglobulin E / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011485:Protein Binding / Q000276:immunology; D011995:Recombination, Genetic / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D014158:Transcription, Genetic / Q000276:immunology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D051820:TCF Transcription Factors; C544913:Tcf7l1 protein, mouse; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D015847:Interleukin-4; D007073:Immunoglobulin E; D004247:DNA; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase