Telomere-dependent replicative senescence of B and T cells from patients with type 1a common variable immunodeficiency

Marcella Visentini, Maria Cagliuso, Valentina Conti, Maurizio Carbonari, Debora Mancaniello, Marina Cibati, Giulia Siciliano, Ezio Giorda, Baerbel Keller, Klaus Warnatz, Massimo Fiorilli, Isabella Quinti

Research output: Contribution to journalArticle

Abstract

A subset of patients with common variable immunodeficiency (CVID), group 1a of the Freiburg classification, is characterized by increased B cells expressing low levels of CD21 (CD21low), lymphoproliferation and autoimmunity. The CD21low B cells have been shown to be profoundly anergic, and defects of BCR-mediated calcium signaling and of T cells have been described in CVID 1a. We found that also the classical naïve B cells from CVID 1a patients, but not from CVID non-1a patients, proliferated poorly. The B cells of CVID 1a patients had a reduced capacity to divide reminiscent of the proliferative arrest associated with replicative senescence. Thus, we investigated whether lymphocyte dysfunction in CVID 1a was related to telomere-dependent replicative senescence, and found that both the B and the T cells from CVID 1a patients had significantly shorter telomeres compared with B and T cells from CVID non-1a patients. Telomere lengths in B and T cells were significantly correlated, indicating that the rate of telomere attrition in lymphocytes is an individual characteristic of CVID patients. Our findings suggest that telomere-dependent replicative senescence contributes to the immune dysfunction of CVID 1a patients, and may provide an important clue for a better understanding of the pathogenesis of CVID.

Original languageEnglish
Pages (from-to)854-862
Number of pages9
JournalEuropean Journal of Immunology
Volume41
Issue number3
DOIs
Publication statusPublished - Mar 2011

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Keywords

  • Anergy
  • Common variable immunodeficiency
  • Telomeres

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Visentini, M., Cagliuso, M., Conti, V., Carbonari, M., Mancaniello, D., Cibati, M., Siciliano, G., Giorda, E., Keller, B., Warnatz, K., Fiorilli, M., & Quinti, I. (2011). Telomere-dependent replicative senescence of B and T cells from patients with type 1a common variable immunodeficiency. European Journal of Immunology, 41(3), 854-862. https://doi.org/10.1002/eji.201040862