Impaired germinal center reaction in mice with short telomeres.
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.
Herrera
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Department of Immunology and Oncology, Centro Nacional de Biotecnología-CSIC, Campus Cantoblanco, E-28049, Madrid, Spain.
Martínez-A
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C
Blasco
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MA
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000378:metabolism*; D002453:Cell Cycle; D002875:Chromosomes; D005434:Flow Cytometry; D018858:Germinal Center / Q000201:enzymology / Q000378:metabolism*; D006651:Histocytochemistry; D007114:Immunization; D017404:In Situ Hybridization, Fluorescence; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D008934:Mitogens / Q000494:pharmacology; D013154:Spleen / Q000201:enzymology / Q000276:immunology; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000276:immunology / Q000378:metabolism*
D008070:Lipopolysaccharides; D008934:Mitogens; D019098:Telomerase