Common variable immunodeficiency is associated with defective functions of dendritic cells

Bayry, Jagadeesh; Lacroix‐Desmazes, Sébastien; Kazatchkine, Michel D.; Galicier, Lionel; Lepelletier, Yves; Webster, David; Lévy, Yves; Eibl, Martha M.; Oksenhendler, Éric; Hermine, Olivier; Kaveri, Srini V.

doi:10.1182/blood-2004-04-1325

Cited by 121 publications

(77 citation statements)

References 24 publications

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“…First, the DC group is in charge of the antigen presentation to other cells, including B-lymphocytes. A reduction in the DC number would have a negative influence in the B-lymphocyte production of immunoglobulins, which would imply a higher sensitivity to bacterial infections (12). Second, a decrease of central memory (CD45RAÀ, CCR7þ) and effector memory (CD45RAÀ, CCR7À) CD8þ T-cell as well as increased of final effector (CD45RAþ, CCR7À) CD8þ Tcell has been reported recently in a patient with Good's Syndrome (13).…”

Section: Discussionmentioning

confidence: 99%

Persistence of immunological alterations after thymectomy in Good's syndrome: A clue to its pathogenesis

Vega

Velasco‐Tirado

Pozo-Rosado

et al. 2011

Cytometry Part B Clinical

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Analyzing the phenotypic characterization of the immune system cells involved in the pathogenesis of immunodeficiency with thymoma (Good's syndrome) is difficult due to the low number of studies on that subject. We describe the immunological alterations observed in a case of Good's syndrome, and we summarize the pathogenic explanations found in the literature. V C 2011 International Clinical Cytometry Society

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Section: Discussionmentioning

confidence: 99%

Persistence of immunological alterations after thymectomy in Good's syndrome: A clue to its pathogenesis

Vega

Velasco‐Tirado

Pozo-Rosado

et al. 2011

Cytometry Part B Clinical

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“…Over the past decades, a number of studies have investigated immune defects in CVID. Although T cell subsets are perturbed (61,62), T cell activation (9), proliferation (63), and cytokine production are subnormal (64,65), apoptosis is enhanced (12,66), and monocyte dendritic cell defects are present (13,14); the defining hallmark of the disease is hypogammaglobulinemia and the lack of functioning B cells. Based on this characteristic, investigators have used a number of in vitro B cell functional studies to stratify patients into those with nonfunctional B cells, poorly functioning B cells or more normally responsive B cells (67)(68)(69).…”

Section: Discussionmentioning

confidence: 99%

“…Many patients have recurrent sinopulmonary infections, but some have gastrointestinal inflammation or autoimmune disease as the first symptom (1,5,6). CVID has been viewed as a heterogeneous group of genetic disorders, because in addition to the clinical variability and range of age at diagnosis, patients have T cell-, cytokine-, and monocyte-derived dendritic cell defects, in addition to the profound lack of Ab production (7)(8)(9)(10)(11)(12)(13)(14). There has been an intensive search for genes which, when mutated, could lead to the CVID phenotype.…”

Section: Ommon Variable Immunodeficiency (Cvid)mentioning

confidence: 99%

TLR9 Activation Is Defective in Common Variable Immune Deficiency

Cunningham‐Rundles

Radigan

Knight

et al. 2006

The Journal of Immunology

109

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Common variable immune deficiency (CVID) is a primary immune deficiency characterized by low levels of serum immune globulins, lack of Ab, and reduced numbers of CD27+ memory B cells. Although T, B, and dendritic cell defects have been described, for the great majority, genetic causes have not been identified. In these experiments, we investigated B cell and plasmacytoid dendritic cell activation induced via TLR9, an intracellular recognition receptor that detects DNA-containing CpG motifs from viruses and bacteria. CpG-DNA activates normal B cells by the constitutively expressed TLR9, resulting in cytokine secretion, IgG class switch, immune globulin production, and potentially, the preservation of long-lived memory B cells. We found that CpG-DNA did not up-regulate expression of CD86 on CVID B cells, even when costimulated by the BCR, or induce production of IL-6 or IL-10 as it does for normal B cells. TLR9, found intracytoplasmically and on the surface of oligodeoxynucleotide-activated normal B cells, was deficient in CVID B cells, as was TLR9 mRNA. TLR9 B cell defects were not related to proportions of CD27+ memory B cells. CpG-activated CVID plasmacytoid dendritic cells did not produce IFN-α in normal amounts, even though these cells contained abundant intracytoplasmic TLR9. No mutations or polymorphisms of TLR9 were found. These data show that there are broad TLR9 activation defects in CVID which would prevent CpG-DNA-initiated innate immune responses; these defects may lead to impaired responses of plasmacytoid dendritic cells and loss of B cell function.

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“…Although various abnormalities in number and function of T cells (3)(4)(5)(6)(7), B cells (8)(9)(10)(11)(12)(13), and dendritic cells (14)(15)(16) have been described, the immunopathological mechanism leading to disturbed Ab production in CVID patients has not yet been defined.…”

Section: Ommon Variable Immunodeficiency (Cvid) Is a Clinically Hetmentioning

confidence: 99%

Characterization of Lymphocyte Subsets in Patients with Common Variable Immunodeficiency Reveals Subsets of Naive Human B Cells Marked by CD24 Expression

Vlková

Froňková

Kanderová

et al. 2010

The Journal of Immunology

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Increased proportions of naive B cell subset and B cells defined as CD27negCD21negCD38neg are frequently found in patients with common variable immunodeficiency (CVID) syndrome. Current methods of polychromatic flow cytometry and PCR-based detection of κ deletion excision circles allow for fine definitions and replication history mapping of infrequent B cell subsets. We have analyzed B cells from 48 patients with CVID and 49 healthy controls to examine phenotype, frequency, and proliferation history of naive B cell subsets. Consistent with previous studies, we have described two groups of patients with normal (CVID-21norm) or increased (CVID-21lo) proportions of CD27negCD21negCD38neg B cells. Upon further analyses, we found two discrete subpopulations of this subset based on the expression of CD24. The B cell subsets showed a markedly increased proliferation in CVID-21lo patients as compared with healthy controls, suggesting developmental arrest rather than increased bone marrow output. Furthermore, when we analyzed CD21pos naive B cells, we found two different subpopulations based on IgM and CD24 expression. They correspond to follicular (FO) I and FO II cells previously described in mice. FO I subset is significantly underrepresented in CVID-21lo patients. A comparison of the replication history of naive B cell subsets in CVID patients and healthy controls implies refined naive B cell developmental scheme, in which human transitional B cells develop into FO II and FO I. We propose that the CD27negCD21negCD38neg B cells increased in some of the CVID patients originate from the two FO subsets after loss of CD21 expression.

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Common variable immunodeficiency is associated with defective functions of dendritic cells

Abstract: Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and defects in T-cell functions that could be primary or secondary. We addressed whether CVID is associated with impairment in the dendritic cell

Cited by 121 publications

References 24 publications

Persistence of immunological alterations after thymectomy in Good's syndrome: A clue to its pathogenesis

Persistence of immunological alterations after thymectomy in Good's syndrome: A clue to its pathogenesis

TLR9 Activation Is Defective in Common Variable Immune Deficiency

Characterization of Lymphocyte Subsets in Patients with Common Variable Immunodeficiency Reveals Subsets of Naive Human B Cells Marked by CD24 Expression

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