Effect of age on the immunoglobulin class switch

Research output: Contribution to journalReview article

31 Scopus citations

Abstract

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-κ or Blimp-1 in old vs young stimulated B cells.

Original languageEnglish (US)
Pages (from-to)297-320
Number of pages24
JournalCritical reviews in immunology
Volume24
Issue number5
DOIs
StatePublished - Dec 1 2004

Keywords

  • Aging
  • Antibody production
  • B cells
  • Class switch recombination (CSR)
  • Transcription factors

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Effect of age on the immunoglobulin class switch'. Together they form a unique fingerprint.

  • Cite this