Impaired germinal center reaction in mice with short telomeres

EMBO J. 2000 Feb 1;19(3):472-81. doi: 10.1093/emboj/19.3.472.

Abstract

Reduction of germinal center reactivity is a landmark of immunosenescence and contributes to immunological dysfunction in the elderly. Germinal centers (GC) are characterized by extensive clonal expansion and selection of B lymphocytes to generate the pool of memory B cells. Telomere maintenance by telomerase has been proposed to allow the extensive proliferation undergone by B lymphocytes in the GC during the immune response. We show here that late generation mTR(-/-) mice, which lack the mouse telomerase RNA (mTR) and have short telomeres, present a dramatic reduction in GC number following antigen immunization. Upon immunization with an antigen, wild-type splenocyte telomeres are elongated and this is accompanied by a high expression of the telomerase catalytic subunit in the spleen GC. In contrast, telomerase-deficient mTR(-/-) splenocytes show telomere shortening after immunization, presumably due to cell proliferation in the absence of telomerase. All together, these results demonstrate the importance of telomere maintenance for antibody-mediated immune responses and support the notion that telomere elongation detected in wild-type spleens following immunization is mediated by telomerase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • B-Lymphocytes / metabolism*
  • Cell Cycle
  • Chromosomes
  • Flow Cytometry
  • Germinal Center / enzymology
  • Germinal Center / metabolism*
  • Histocytochemistry
  • Immunization
  • In Situ Hybridization, Fluorescence
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Knockout
  • Mitogens / pharmacology
  • Spleen / enzymology
  • Spleen / immunology
  • Telomerase / genetics*
  • Telomere / immunology
  • Telomere / metabolism*

Substances

  • Lipopolysaccharides
  • Mitogens
  • Telomerase