Effect of age on the immunoglobulin class switch.
Aging represents a complex remodelling in which both specific and innate immunity deteriorate. Age-related changes in humoral immunity involve reduced vaccine responses and increased production of auto-antibodies. Although T-cell alterations play a significant role in age-related humoral immune changes, alterations in B cells also occur. In this review, we provide an overview of age-related changes in B-cell functions and markers, including transcription factors, and also discuss controversies in the field of B-cell aging. We summarize our recent results, showing that splenic B cells from senescent mice are deficient in production of secondary isotypes (IgG1, IgG2a, IgG3, IgE), class switch recombination (CSR), and expression of the transcription factor E47. We also demonstrate that there is more Id2 (a negative regulator of E47) in old activated B cells. E47 is required for CSR, at least in part, via expression of activation-induced cytidine deaminase (AID). Our studies show that impaired induction of E47, and, subsequently, AID, contribute to poor CSR and production of secondary isotypes in senescence. We also present new data indicating the absence of DNA switch region excision circles for CSR in old activated B cells, confirming the location of the defect at the DNA endonucleolytic step. And, finally, we show that there is no change in NF-kappaB or Blimp-1 in old vs young stimulated B cells.
Frasca
Daniela
D
Department of Microbiology and Immunology, University of Miami School of Medicine, P.O. Box 016960 (R-138), Miami, FL 33101, USA.
Riley
Richard L
RL
Blomberg
Bonnie B
BB
D000367:Age Factors; D000375:Aging; D000818:Animals; D000917:Antibody Formation / Q000276:immunology / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D004268:DNA-Binding Proteins / Q000502:physiology; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000502:physiology; D051757:PAX5 Transcription Factor; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D051757:PAX5 Transcription Factor; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins; D014157:Transcription Factors; C497281:PAX5 protein, human; C497282:Pax5 protein, mouse; C513258:Prdm1 protein, mouse; C407909:TCF3 protein, human; C087042:PRDM1 protein, human