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

Eur J Immunol. 2011 Mar;41(3):854-62. doi: 10.1002/eji.201040862. Epub 2011 Feb 2.


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 (CD21(low) ), lymphoproliferation and autoimmunity. The CD21(low) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • Calcium Signaling / immunology
  • Case-Control Studies
  • Cellular Senescence / immunology
  • Common Variable Immunodeficiency / classification
  • Common Variable Immunodeficiency / etiology
  • Common Variable Immunodeficiency / immunology*
  • Common Variable Immunodeficiency / pathology
  • Female
  • Humans
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Receptors, Complement 3d / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • Telomere / genetics
  • Telomere / pathology*
  • Young Adult


  • Receptors, Complement 3d