Effect of age on the immunoglobulin class switch

被引:30
作者
Frasca, D [1 ]
Riley, RL [1 ]
Blomberg, BB [1 ]
机构
[1] Univ Miami, Sch Med, Dept Microbiol & Immunol, Miami, FL 33101 USA
关键词
aging; antibody production; B cells; class switch recombination (CSR); transcription factors;
D O I
10.1615/CritRevImmunol.v24.i5.10
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 autoantibodies. 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, lgE), 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 endonudeolytic step. And, finally, we show that there is no change in NF-kappaB or Blimp-1 in old vs young stimulated B cells.
引用
收藏
页码:297 / 320
页数:24
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