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 language | English |
|---|---|
| Pages (from-to) | 854-862 |
| Number of pages | 9 |
| Journal | European Journal of Immunology |
| Volume | 41 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2011 |
Fingerprint
Keywords
- Anergy
- Common variable immunodeficiency
- Telomeres
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
Telomere-dependent replicative senescence of B and T cells from patients with type 1a common variable immunodeficiency. / Visentini, Marcella; Cagliuso, Maria; Conti, Valentina; Carbonari, Maurizio; Mancaniello, Debora; Cibati, Marina; Siciliano, Giulia; Giorda, Ezio; Keller, Baerbel; Warnatz, Klaus; Fiorilli, Massimo; Quinti, Isabella.
In: European Journal of Immunology, Vol. 41, No. 3, 03.2011, p. 854-862.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Telomere-dependent replicative senescence of B and T cells from patients with type 1a common variable immunodeficiency
AU - Visentini, Marcella
AU - Cagliuso, Maria
AU - Conti, Valentina
AU - Carbonari, Maurizio
AU - Mancaniello, Debora
AU - Cibati, Marina
AU - Siciliano, Giulia
AU - Giorda, Ezio
AU - Keller, Baerbel
AU - Warnatz, Klaus
AU - Fiorilli, Massimo
AU - Quinti, Isabella
PY - 2011/3
Y1 - 2011/3
N2 - 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.
AB - 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.
KW - Anergy
KW - Common variable immunodeficiency
KW - Telomeres
UR - http://www.scopus.com/inward/record.url?scp=79951791830&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79951791830&partnerID=8YFLogxK
U2 - 10.1002/eji.201040862
DO - 10.1002/eji.201040862
M3 - Article
C2 - 21287551
AN - SCOPUS:79951791830
VL - 41
SP - 854
EP - 862
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 3
ER -