title: Telomere-dependent replicative senescence of B and T cells from patients with type 1a common variable immunodeficiency.
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 (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.
authors.affiliation: Department of Clinical Immunology, Sapienza University of Rome, Rome, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Visentini
authors.forename: Maria
authors.initials: M
authors.lastname: Cagliuso
authors.forename: Valentina
authors.initials: V
authors.lastname: Conti
authors.forename: Maurizio
authors.initials: M
authors.lastname: Carbonari
authors.forename: Debora
authors.initials: D
authors.lastname: Mancaniello
authors.forename: Marina
authors.initials: M
authors.lastname: Cibati
authors.forename: Giulia
authors.initials: G
authors.lastname: Siciliano
authors.forename: Ezio
authors.initials: E
authors.lastname: Giorda
authors.forename: Baerbel
authors.initials: B
authors.lastname: Keller
authors.forename: Klaus
authors.initials: K
authors.lastname: Warnatz
authors.forename: Massimo
authors.initials: M
authors.lastname: Fiorilli
authors.forename: Isabella
authors.initials: I
authors.lastname: Quinti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D020013:Calcium Signaling / Q000276:immunology; D016022:Case-Control Studies; D016922:Cellular Senescence / Q000276:immunology; D017074:Common Variable Immunodeficiency / Q000145:classification / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D017464:Receptors, Complement 3d / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016615:Telomere / Q000235:genetics / Q000473:pathology*; D055815:Young Adult
chemical_list: D017464:Receptors, Complement 3d