Abstract
Background Chronic granulomatous disease (CGD) is a primary immune deficiency characterized by a defect in reactive oxygen species production. Although the effect of CGD mainly reflects on the phagocytic compartment, B-cell responses are also impaired in patients with CGD. Objective We sought to investigate how defective gp91phox expression in patients with CGD and CGD carriers might affect the B-cell compartment and maintenance of long-term memory. Methods We studied the B-cell compartment of patients with CGD in terms of phenotype and ability to produce reactive oxygen species and proliferate on stimuli differently directed to the B-cell receptor and Toll-like receptor 9. We further studied their capacity to maintain long-term memory by measuring cellular and serologic responses to measles. Results We show that the memory B-cell compartment is impaired among patients with CGD, as indicated by reduced total (CD19+CD27+) and resting (CD19+CD27+CD21+) memory B cells in parallel to increased naive (CD19+CD27-IgD+) B-cell frequencies. Data on CGD carriers reveal that such alterations are related to gp91phox expression. Moreover, proliferative capabilities of B cells on selective in vitro stimulation of B-cell receptor or Toll-like receptor 9 pathways were reduced in patients with CGD compared with those seen in age-matched healthy control subjects. Significantly lower measles-specific antibody levels and antibody-secreting cell numbers were also observed, indicating a poor ability to maintain long-term memory in these patients. Conclusion Altogether, our data suggest that patients with CGD present a defective B-cell compartment in terms of frequencies of memory B cells, response to in vitro stimulation, and maintenance of long-term antigen-specific memory.
| Original language | English |
|---|---|
| Pages (from-to) | 753-761.e2 |
| Journal | Journal of Allergy and Clinical Immunology |
| Volume | 135 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 1 2015 |
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Keywords
- B cell
- Chronic granulomatous disease
- long-term memory
- measles
- memory B-cell compartment
- proliferation
- reactive oxygen species deficiency
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Medicine(all)
Cite this
Defective B-cell proliferation and maintenance of long-term memory in patients with chronic granulomatous disease. / Cotugno, Nicola; Finocchi, Andrea; Cagigi, Alberto; Di Matteo, Gigliola; Chiriaco, Maria; Di Cesare, Silvia; Rossi, Paolo; Aiuti, Alessandro; Palma, Paolo; Douagi, Iyadh.
In: Journal of Allergy and Clinical Immunology, Vol. 135, No. 3, 01.03.2015, p. 753-761.e2.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Defective B-cell proliferation and maintenance of long-term memory in patients with chronic granulomatous disease
AU - Cotugno, Nicola
AU - Finocchi, Andrea
AU - Cagigi, Alberto
AU - Di Matteo, Gigliola
AU - Chiriaco, Maria
AU - Di Cesare, Silvia
AU - Rossi, Paolo
AU - Aiuti, Alessandro
AU - Palma, Paolo
AU - Douagi, Iyadh
PY - 2015/3/1
Y1 - 2015/3/1
N2 - Background Chronic granulomatous disease (CGD) is a primary immune deficiency characterized by a defect in reactive oxygen species production. Although the effect of CGD mainly reflects on the phagocytic compartment, B-cell responses are also impaired in patients with CGD. Objective We sought to investigate how defective gp91phox expression in patients with CGD and CGD carriers might affect the B-cell compartment and maintenance of long-term memory. Methods We studied the B-cell compartment of patients with CGD in terms of phenotype and ability to produce reactive oxygen species and proliferate on stimuli differently directed to the B-cell receptor and Toll-like receptor 9. We further studied their capacity to maintain long-term memory by measuring cellular and serologic responses to measles. Results We show that the memory B-cell compartment is impaired among patients with CGD, as indicated by reduced total (CD19+CD27+) and resting (CD19+CD27+CD21+) memory B cells in parallel to increased naive (CD19+CD27-IgD+) B-cell frequencies. Data on CGD carriers reveal that such alterations are related to gp91phox expression. Moreover, proliferative capabilities of B cells on selective in vitro stimulation of B-cell receptor or Toll-like receptor 9 pathways were reduced in patients with CGD compared with those seen in age-matched healthy control subjects. Significantly lower measles-specific antibody levels and antibody-secreting cell numbers were also observed, indicating a poor ability to maintain long-term memory in these patients. Conclusion Altogether, our data suggest that patients with CGD present a defective B-cell compartment in terms of frequencies of memory B cells, response to in vitro stimulation, and maintenance of long-term antigen-specific memory.
AB - Background Chronic granulomatous disease (CGD) is a primary immune deficiency characterized by a defect in reactive oxygen species production. Although the effect of CGD mainly reflects on the phagocytic compartment, B-cell responses are also impaired in patients with CGD. Objective We sought to investigate how defective gp91phox expression in patients with CGD and CGD carriers might affect the B-cell compartment and maintenance of long-term memory. Methods We studied the B-cell compartment of patients with CGD in terms of phenotype and ability to produce reactive oxygen species and proliferate on stimuli differently directed to the B-cell receptor and Toll-like receptor 9. We further studied their capacity to maintain long-term memory by measuring cellular and serologic responses to measles. Results We show that the memory B-cell compartment is impaired among patients with CGD, as indicated by reduced total (CD19+CD27+) and resting (CD19+CD27+CD21+) memory B cells in parallel to increased naive (CD19+CD27-IgD+) B-cell frequencies. Data on CGD carriers reveal that such alterations are related to gp91phox expression. Moreover, proliferative capabilities of B cells on selective in vitro stimulation of B-cell receptor or Toll-like receptor 9 pathways were reduced in patients with CGD compared with those seen in age-matched healthy control subjects. Significantly lower measles-specific antibody levels and antibody-secreting cell numbers were also observed, indicating a poor ability to maintain long-term memory in these patients. Conclusion Altogether, our data suggest that patients with CGD present a defective B-cell compartment in terms of frequencies of memory B cells, response to in vitro stimulation, and maintenance of long-term antigen-specific memory.
KW - B cell
KW - Chronic granulomatous disease
KW - long-term memory
KW - measles
KW - memory B-cell compartment
KW - proliferation
KW - reactive oxygen species deficiency
UR - http://www.scopus.com/inward/record.url?scp=84924420351&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84924420351&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2014.07.012
DO - 10.1016/j.jaci.2014.07.012
M3 - Article
C2 - 25175493
AN - SCOPUS:84924420351
VL - 135
SP - 753-761.e2
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 3
ER -