B cell subsets in healthy children: Reference values for evaluation of B cell maturation process in peripheral blood

Piątosa, Barbara; Wolska-Kuśnierz, Beata; Pac, Małgorzata; Siewiera, Katarzyna; Gałkowska, Ewa; Bernatowska, Ewa

doi:10.1002/cyto.b.20536

Cited by 134 publications

(151 citation statements)

References 41 publications

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“…As described in the current literature, transitional B-cells can be separated by IgM111 and CD38111 coexpression (5,17,18,20,21). In the same analysis plot, plasmablasts can be identified based on CD38111 expression (cave: difference to immature transitional in Fig.…”

Section: Panel Design and Gating Strategymentioning

confidence: 77%

“…In the same analysis plot, plasmablasts can be identified based on CD38111 expression (cave: difference to immature transitional in Fig. 4E) and absence of surface IgM (17,18). Moreover, CD271CD1381 peripheral plasma cells can be detected (19).…”

Section: Panel Design and Gating Strategymentioning

confidence: 85%

“…B-cell subpopulations: B-cells (CD191) were separated from the lymphocyte collection gate. The combination of CD21 versus CD27 allowed the identification of immature (6,17,18), CD21 low (6,18) and (total) memory B-cells. As a baseline for CD211 or CD271 cells, double negative immature cells were used.…”

Section: Panel Design and Gating Strategymentioning

confidence: 99%

See 2 more Smart Citations

Eight-color immunophenotyping of T-, B-, and NK-cell subpopulations for characterization of chronic immunodeficiencies

et al. 2014

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Section: Panel Design and Gating Strategymentioning

confidence: 77%

Section: Panel Design and Gating Strategymentioning

confidence: 85%

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Eight-color immunophenotyping of T-, B-, and NK-cell subpopulations for characterization of chronic immunodeficiencies

et al. 2014

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“…Our data are in line with previously published B-cell subset reference values. [15][16][17][18][19] Memory B cells were reduced in the majority of CVID patients and mainly involved GCdependent maturation pathways. IPH patients less frequently showed abnormalities in memory B-cell subsets, in line with our hypothesis that most of these patients suffer from plasma-cell survival or homing defects.…”

Section: Discussionmentioning

confidence: 99%

Common variable immunodeficiency and idiopathic primary hypogammaglobulinemia: two different conditions within the same disease spectrum

et al. 2013

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ABSTRACTical practice, but information concerning the prevalence and the clinical and immunological characteristics is not available. It is important to obtain insight into the frequency and severity of the clinical complications of IPH, to clarify whether IPH is a clinically relevant antibody deficiency, and to develop appropriate treatment strategies. In addition, analysis of immunological parameters will enable the comparison of pathophysiological aspects of IPH and CVID.Therefore, we aimed to determine the position of IPH in the spectrum of idiopathic antibody deficiencies through clinical and immunological comparison with CVID. First, we recorded the patients with the clinical phenotypes as established by Chapel et al. 2,7 In addition, we performed flow cytometric immunophenotyping in order to analyze T-cell dependent and independent memory B-cell subset counts 8 and blood B-cell patterns, which are associated with differences in pathophysiological background. 9 Methods PatientsPeripheral blood samples and clinical data were collected for 44 CVID patients and 21 IPH patients. IPH was diagnosed if patients had a reduction of IgG at least 2 SD below the mean for age, an onset of the immunodeficiency after two years of age, exclusion of defined causes of hypogammaglobulinemia and if they did not fulfill the CVID diagnostic criteria with respect to a reduction of two immunoglobulin isotypes and/or a reduced response to vaccination. The group of CVID patients includes the 37 patients who were reported in our original description of the B-cell patterns. 9 In addition, we collected blood from 130 healthy age-matched controls and 26 cord blood samples. This study was approved by the Medical Ethics Committee of the Erasmus MC. Clinical phenotypingClinical data were collected from all IPH and CVID patients to record their clinical phenotypes as previously described by Chapel et al. 2,5 These phenotypes are: 1) no disease-related complications (infections only); 2) autoimmune cytopenias; 3) polyclonal lymphoproliferation (granuloma/LIP/persistent unexplained lympadenopathy); and 4) unexplained persistent enteropathy. In addition, data were collected concerning the frequency and severity of infections and modes of treatment. Pneumococcal polysaccharide vaccination responses were interpreted according to Borgers et al. 10 as an adequate response to half of the measured pneumococcal serotypes. Flow cytometric analysis and assignment of B-cell patternsSix-color flow cytometric immunophenotyping of peripheral blood was performed on a CantoII (BD Biosiences) and data were analyzed using FACS Diva software (BD Biosiences). The following monoclonal antibodies were used: CD19-PerCP-Cy5.5, CD19-PE-Cy7, CD19-APC (all SJ25C1), CD5-APC ( L17F12 ), CD45-PerCP (2D1), CD19-APC (SJ25C1), CD38-PE, CD38-APC and CD38-PE-Cy7 ( HB7), CD27-APC (L128), CD3-PerCP-Cy5.5 (SK7) and CD8-APC-Cy7 (SK1) (all from BD Biosciences), polyclonal IgD-FITC, IgD-PE and IgM-PE (all from Southern Biotechnologies), polyclonal IgG-FITC (Kallestad), IgA-FITC a...

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“…Absolute counts of all cell subsets were calculated from the leukocyte count obtained from the analyzer XT 2000i (Sysmex, Japan). A comparative analysis was done with a group of 111 healthy children, aged 5 months to 5 years, whose peripheral blood B lymph cell immunophenotyping had been carried out by Piątosa et al (9) and served to elaborate the reference values for pediatric populations at different age groups.…”

Section: Methodsmentioning

confidence: 99%

Impaired Antigen-Specific Immune Response to Vaccines in Children with Antibody Production Defects

Szczawińska-Popłonyk

Bręborowicz

Samara

et al. 2015

Clin Vaccine Immunol

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The impaired synthesis of antigen-specific antibodies, which is indispensable for an adaptive immune response to infections, is a fundamental pathomechanism that leads to clinical manifestations in children with antibody production defects. The aim of this study was to evaluate the synthesis of antigen-specific antibodies following immunization in relation to peripheral blood B cell subsets in young children with hypogammaglobulinemia. Twenty-two children, aged from 8 to 61 months, with a deficiency in one or more major immunoglobulin classes participated in the study. Postvaccination antibodies against tetanus and diphtheria toxoids, the surface antigen of the hepatitis B virus, and the capsular Haemophilus influenzae type b polysaccharide antigen were assessed along with an immunophenotypic evaluation of peripheral blood B lymph cell maturation. A deficiency of antibodies against the tetanus toxoid was assessed in 73% of cases and that against the diphtheria toxoid was assessed in 68% of cases, whereas a deficiency of antibodies against the surface antigen of the hepatitis B virus was revealed in 59% of the children included in the study. A defective response to immunization with a conjugate vaccine with the Haemophilus influenzae type b polysaccharide antigen was demonstrated in 55% of hypogammaglobulinemic patients. Increased proportions of transitional B lymph cells and an accumulation of plasmablasts accompanied antibody deficiencies. The defective response to vaccine protein and polysaccharide antigens is a predominating disorder of humoral immunity in children with hypogammaglobulinemia and may result from a dysfunctional state of the cellular elements of the immune system. A ntibody production defects are the most common category of pediatric primary immunodeficiencies (PIDs) (1, 2). The hallmark of these immunodeficiency conditions is the defective production of antigen-specific antibodies that are an indispensable element of the adaptive immune response to pathogens (3, 4). While the poor response to vaccines is another feature of humoral PIDs, the ability to synthesize postvaccination antibodies against toxoids and polysaccharides is the most specific expression of the immune response to antigens. In the evaluation of the immune response associated with antibody production, the response to vaccination against hepatitis B is not routinely recommended because of the large proportion of adults, up to between 1% and 3% of vaccinated individuals, who do not effectively synthesize antibodies against hepatitis B virus surface antigen (HBs). In infants and children, the efficiency of recombinant vaccines against hepatitis B, assessed on the basis of postvaccination anti-HBs antibody concentration over 10 mIU/ml, is estimated at 85% to 100% (5, 6). The minimal protective level of neutralizing antibodies against diphtheria and tetanus toxoids has been estimated at 0.01 to 0.1 IU/ml, whereas to achieve long-term immunity, a concentration of specific antibodies, up to 1.0 IU/ml, may be required. The synthesis of...

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B cell subsets in healthy children: Reference values for evaluation of B cell maturation process in peripheral blood

Cited by 134 publications

References 41 publications

Eight-color immunophenotyping of T-, B-, and NK-cell subpopulations for characterization of chronic immunodeficiencies

Eight-color immunophenotyping of T-, B-, and NK-cell subpopulations for characterization of chronic immunodeficiencies

Common variable immunodeficiency and idiopathic primary hypogammaglobulinemia: two different conditions within the same disease spectrum

Impaired Antigen-Specific Immune Response to Vaccines in Children with Antibody Production Defects

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