Severe deficiency of switched memory B cells (CD27+IgM−IgD−) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease

Warnatz, Klaus; Denz, Axel; Dräger, Ruth; Braun, M; Groth, Christoph; Wolff-Vorbeck, Guido; Eibel, Hermann; Schlesier, Michael; Peter, Hans

doi:10.1182/blood.v99.5.1544

Cited by 545 publications

(538 citation statements)

References 49 publications

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“…In addition to XLP, several other conditions are characterized by a deficiency of memory B cells and hypogammaglobulinemia, including CVID (20,22,43) and post-HSCT (25,44). Humoral immune responses are also reduced in neonates (45).…”

Section: Transitional B Cells Are Expanded In Humoral Immunodeficiencmentioning

confidence: 99%

“…1a) (21,26). It was recently reported that some patients with CVID not only lacked memory B cells, but also B cells with an immature phenotype were occasionally detected (20). This prompted us to analyze the B cell compartment of XLP patients in greater detail to determine whether their CD27 Ϫ B cells were phenotypically similar to those in normal donors.…”

Section: Cd24 High Cd38 High B Cells Are Expanded In Xlpmentioning

confidence: 99%

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Expansion of Functionally Immature Transitional B Cells Is Associated with Human-Immunodeficient States Characterized by Impaired Humoral Immunity

Cuss

Avery

Cannons

et al. 2006

The Journal of Immunology

177

188

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X-linked lymphoproliferative disease (XLP) is a severe immunodeficiency associated with a marked reduction in circulating memory B cells. Our investigation of the B cell compartment of XLP patients revealed an increase in the frequency of a population of B cells distinct from those previously defined. This population displayed increased expression of CD10, CD24, and CD38, indicating that it could consist of circulating immature/transitional B cells. Supporting this possibility, CD10+CD24highCD38high B cells displayed other immature characteristics, including unmutated Ig V genes and elevated levels of surface IgM; they also lacked expression of Bcl-2 and a panel of activation molecules. The capacity of CD24highCD38high B cells to proliferate, secrete Ig, and migrate in vitro was greatly reduced compared with mature B cell populations. Moreover, CD24highCD38high B cells were increased in the peripheral blood of neonates, patients with common variable immunodeficiency, and patients recovering from hemopoietic stem cell transplant. Thus, an expansion of functionally immature B cells may contribute to the humoral immunodeficient state that is characteristic of neonates, as well as patients with XLP or common variable immunodeficiency, and those recovering from a stem cell transplant. Further investigation of transitional B cells will improve our understanding of human B cell development and how alterations to this process may precipitate immunodeficiency or autoimmunity.

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Section: Transitional B Cells Are Expanded In Humoral Immunodeficiencmentioning

confidence: 99%

Section: Cd24 High Cd38 High B Cells Are Expanded In Xlpmentioning

confidence: 99%

Expansion of Functionally Immature Transitional B Cells Is Associated with Human-Immunodeficient States Characterized by Impaired Humoral Immunity

Cuss

Avery

Cannons

et al. 2006

The Journal of Immunology

177

188

View full text Add to dashboard Cite

show abstract

“…Brouet et al [7] were the first to recognize the potential lack of B cells bearing CD27 in CVID, and this was amplified by Agematsu and Ochs [8]. Subsequently, the lack of switched memory B cells (B cells of the CD27 + , IgM-IgDphenotype) were characteristic of a large proportion of subjects with CVID, and that there relative lack of these cells could be used to divide patients into two clinically and immunologically different groups [3,9,10]. The lack of switched memory B cells was also found related to a lack of antibody production to pneumococcal vaccine, and interestingly, in these and other studies, also to the presence of autoimmune disease [11,12].…”

Section: Granulomatous Disease Autoimmunity and Memory B Cell Phenomentioning

confidence: 99%

Autoimmune Manifestations in Common Variable Immunodeficiency

Cunningham‐Rundles

2008

J Clin Immunol

128

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“…Patients with common variable immunodeficiency (CVID), characterized by recurrent bacterial infections and a failure to make pneumococcal vaccination responses, were recruited as disease controls (n ϭ 28). All patients with CVID satisfied the Pan-American Group for Immunodeficiency and the European Society for Immunodeficiency diagnostic criteria for this condition (25,26). Twenty-five CVID patients were receiving IgG replacement containing exogenous pneumococcal and tetanus Abs.…”

Section: Controls and Patient Groupsmentioning

confidence: 99%

Loss of Discrete Memory B Cell Subsets Is Associated with Impaired Immunization Responses in HIV-1 Infection and May Be a Risk Factor for Invasive Pneumococcal Disease

Hart

Steel

Clark

et al. 2007

The Journal of Immunology

152

154

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Invasive pneumococcal infection is an important cause of morbidity and mortality in HIV-1-infected individuals. B cells play an important role in maintaining serologic memory after infection. IgM memory B cells are significantly reduced in HIV-1-infected patients and their frequency is similar to that observed in other patient groups (splenectomized individuals and patients with primary Ab deficiency) who are also known to have an increased risk of invasive pneumococcal infection. Antiretroviral therapy does not restore marginal zone B cell percentages. Immunization with the 23-valent polysaccharide pneumococcal vaccine shows that HIV-1-infected patients have impaired total IgM and IgG pneumococcal vaccines compared with healthy controls. Loss of switched memory B cells was associated with impaired tetanus toxoid IgG vaccine responses. Results of this study demonstrate that defects in B cell memory subsets are associated with impaired humoral immune responses in HIV-1 patients who are receiving antiretroviral therapy and may be a contributory factor to the increased risk of invasive pneumococcal infection observed in HIV-1 infection.

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Severe deficiency of switched memory B cells (CD27+IgM−IgD−) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease

Cited by 545 publications

References 49 publications

Expansion of Functionally Immature Transitional B Cells Is Associated with Human-Immunodeficient States Characterized by Impaired Humoral Immunity

Expansion of Functionally Immature Transitional B Cells Is Associated with Human-Immunodeficient States Characterized by Impaired Humoral Immunity

Autoimmune Manifestations in Common Variable Immunodeficiency

Loss of Discrete Memory B Cell Subsets Is Associated with Impaired Immunization Responses in HIV-1 Infection and May Be a Risk Factor for Invasive Pneumococcal Disease

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