Defective B-cell proliferation and maintenance of long-term memory in patients with chronic granulomatous disease

Nicola Cotugno, Andrea Finocchi, Alberto Cagigi, Gigliola Di Matteo, Maria Chiriaco, Silvia Di Cesare, Paolo Rossi, Alessandro Aiuti, Paolo Palma, Iyadh Douagi

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)753-761.e2
JournalJournal of Allergy and Clinical Immunology
Volume135
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

Fingerprint

Chronic Granulomatous Disease
Long-Term Memory
B-Lymphocytes
Cell Proliferation
Toll-Like Receptor 9
Aptitude
Measles
Reactive Oxygen Species
Immunoglobulin D
Antibody-Producing Cells
Healthy Volunteers
Cell Count

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 journalArticle

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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

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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.

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