Humans with chronic granulomatous disease maintain humoral immunologic memory despite low frequencies of circulating memory B cells

Moir, Susan; Ravin, Suk See De; Santich, Brian H.; Kim, Jin Young; Posada, Jacqueline G.; Ho, Jason; Buckner, Clarisa M.; Wang, Wei; Kardava, Lela; Garofalo, Mary; Marciano, Beatriz E.; Manischewitz, Jody; King, Lisa R.; Khurana, Surender; Chun, Tae‐Wook; Golding, Hana; Fauci, Anthony S.; Malech, Harry L.

doi:10.1182/blood-2012-05-430959

Cited by 30 publications

(25 citation statements)

References 30 publications

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“…In fact, patients with CGD have been reported to have lower total memory B-cell counts (CD19 1 CD27 1 ) and resting memory B-cell counts (CD19 1 CD10 2 CD21 1 CD27 1 ). 10 In the present study we confirmed these findings.…”

Section: Discussionsupporting

confidence: 91%

“…[3][4][5][6] Although CGD is primarily recognized as an oxidative deficiency of the phagocytic compartment, key cellular pathways, including lymphocyte function, were also shown to link to ROS production. 7,8 Furthermore, patients affected by CGD have been described to present lower frequencies of circulating memory B cells, 9,10 with an intact humoral immunologic memory. 10 This was shown primarily in patients receiving immunosuppressive therapies.…”

mentioning

confidence: 99%

“…7,8 Furthermore, patients affected by CGD have been described to present lower frequencies of circulating memory B cells, 9,10 with an intact humoral immunologic memory. 10 This was shown primarily in patients receiving immunosuppressive therapies. 10 Recent mouse studies showed a direct relation between the B-cell stimulation and the production of ROS.…”

mentioning

confidence: 99%

“…10 This was shown primarily in patients receiving immunosuppressive therapies. 10 Recent mouse studies showed a direct relation between the B-cell stimulation and the production of ROS. Lower activity of the NADPH oxidase could impair B-cell receptor (BCR) signal strength, reducing activation and proliferation of B cells in response to surface immunoglobulin cross-linking.…”

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confidence: 99%

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

Cotugno

Finocchi

Cagigi

et al. 2015

Journal of Allergy and Clinical Immunology

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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 gp91 phox 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 1 CD27 1 ) and resting (CD19 1 CD27 1 CD21 1 ) memory B cells in parallel to increased naive (CD19 1 CD27 2 IgD 1 ) B-cell frequencies. Data on CGD carriers reveal that such alterations are related to gp91 phox 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

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

Cotugno

Finocchi

Cagigi

et al. 2015

Journal of Allergy and Clinical Immunology

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“…Patients with chronic granulomatous disease (CGD) in infancy or childhood often suffer from life-threatening bacterial and fungal infections (45,46); however, it is not known whether susceptibility to viral infections is increased in CGD patients. Recent studies have shown that CGD patients maintain an intact memory response in humoral immunity, with normal serum IgG and influenza-specific Ab levels, although they have reduced numbers of circulating CD27 + memory B cells (47). Moreover, NOX2-deficient T cells show a skewed Th1 response, with augmented IFN-g and decreased IL-4 production (48).…”

Section: Discussionmentioning

confidence: 99%

TLR3-Triggered Reactive Oxygen Species Contribute to Inflammatory Responses by Activating Signal Transducer and Activator of Transcription-1

Yang

Kim

Lee

et al. 2013

The Journal of Immunology

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Intracellular reactive oxygen species (ROS) are essential secondary messengers in many signaling cascades governing innate immunity and cellular functions. TLR3 signaling is crucially involved in antiviral innate and inflammatory responses; however, the roles of ROS in TLR3 signaling remain largely unknown. In this study, we show that TLR3-induced ROS generation is required for the activation of NF-κB, IFN-regulatory factor 3, and STAT1-mediated innate immune responses in macrophages. TLR3 induction led to a rapid increase in ROS generation and a physical association between components of the NADPH oxidase (NOX) enzyme complex (NOX2 and p47phox) and TLR3 via a Ca2+-c-Src tyrosine kinase–dependent pathway. TLR3-induced ROS generation, NOX2, and p47phox were required for the phosphorylation and nuclear translocation of STAT1 and STAT2. TLR3-induced activation of STAT1 contributed to the generation of inflammatory mediators, which was significantly attenuated in NOX2- and p47phox-deficient macrophages, suggesting a role for ROS-STAT1 in TLR3-mediated innate immune responses. Collectively, these results provide a novel insight into the crucial role that TLR3-ROS signaling plays in innate immune responses by activating STAT1.

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Mice Deficient in NOX2 Display Severe Thymic Atrophy, Lymphopenia, and Reduced Lymphopoiesis in a Zymosan-Induced Model of Systemic Inflammation

Endo

Aratani

2020

Inflammation

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Humans with chronic granulomatous disease maintain humoral immunologic memory despite low frequencies of circulating memory B cells

Cited by 30 publications

References 30 publications

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

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

TLR3-Triggered Reactive Oxygen Species Contribute to Inflammatory Responses by Activating Signal Transducer and Activator of Transcription-1

Mice Deficient in NOX2 Display Severe Thymic Atrophy, Lymphopenia, and Reduced Lymphopoiesis in a Zymosan-Induced Model of Systemic Inflammation

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