CD8+HLA-DR+ T lymphocytes are increased in common variable immunodeficiency patients with impaired memory B-cell differentiation

2006 ◽  
Vol 119 (1) ◽  
pp. 51-58 ◽  
Author(s):  
Jean-François Viallard ◽  
Patrick Blanco ◽  
Marc André ◽  
Gabriel Etienne ◽  
François Liferman ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Lymphocytes ◽  
B Cell ◽  
Common Variable Immunodeficiency ◽  
B Cell Differentiation ◽  
Memory B Cell ◽  
Impaired Memory ◽  
Hla Dr ◽  
Common Variable

scholarly journals Single-Cell Atlas of Common Variable Immunodeficiency reveals germinal center-associated epigenetic dysregulation in B cell responses

2021 ◽  
Author(s):  
Javier Rodriguez-Ubreva ◽  
Anna Arutyunyan ◽  
Marc Jan Bonder ◽  
Lucia Del Pino-Molina ◽  
Stephen Clark ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cell ◽  
Single Cell ◽  
Common Variable Immunodeficiency ◽  
Immune Cell ◽  
B Cell Differentiation ◽  
Memory B Cell ◽  
Wide Range ◽  
Mz Twins ◽  
Common Variable

Common variable immunodeficiency (CVID), the most prevalent symptomatic primary immunodeficiency, is characterized by impaired terminal B-cell differentiation and defective antibody responses. Incomplete genetic penetrance and a wide range of phenotypic expressivity in CVID suggest the participation of additional pathogenic mechanisms. Monozygotic (MZ) twins discordant for CVID are uniquely valuable for studying the contribution of epigenetics to the disease. We used single-cell epigenomics and transcriptomics to create a cell census of naive-to-memory B cell differentiation in a pair of CVID-discordant MZ twins. Our analysis identifies DNA methylation, chromatin accessibility and transcriptional defects in memory B cells that mirror defective cell-cell communication defects following activation. These findings were validated in a cohort of CVID patients and healthy donors. Our findings provide a comprehensive multi-omics map of alterations in naive-to-memory B-cell transition in CVID and reveal links between the epigenome and immune cell cross-talk. Our resource, publicly available at the Human Cell Atlas, paves the way for future diagnosis and treatments of CVID patients.

The EUROclass trial: defining subgroups in common variable immunodeficiency

Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 77-85 ◽  
Author(s):  
Claudia Wehr ◽  
Teemu Kivioja ◽  
Christian Schmitt ◽  
Berne Ferry ◽  
Torsten Witte ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Common Variable Immunodeficiency ◽  
Multicenter Trial ◽  
Memory B Cells ◽  
Granulomatous Disease ◽  
B Cell Differentiation ◽  
Cell Subpopulations ◽  
Common Variable

The heterogeneity of common variable immunodeficiency (CVID) calls for a classification addressing pathogenic mechanisms as well as clinical relevance. This European multicenter trial was initiated to develop a consensus of 2 existing classification schemes based on flowcytometric B-cell phenotyping and the clinical course. The clinical evaluation of 303 patients with the established diagnosis of CVID demonstrated a significant coincidence of granulomatous disease, autoimmune cytopenia, and splenomegaly. Phenotyping of B-cell subpopulations confirmed a severe reduction of switched memory B cells in most of the patients that was associated with a higher risk for splenomegaly and granulomatous disease. An expansion of CD21low B cells marked patients with splenomegaly. Lymphadenopathy was significantly linked with transitional B-cell expansion. Based on these findings and pathogenic consideration of B-cell differentiation, we suggest an improved classification for CVID (EUROclass), separating patients with nearly absent B cells (less than 1%), severely reduced switched memory B cells (less than 2%), and expansion of transitional (more than 9%) or CD21low B cells (more than 10%). Whereas the first group contains all patients with severe defects of early B-cell differentiation, severely reduced switched memory B cells indicate a defective germinal center development as found in inducible constimulator (ICOS) or CD40L deficiency. The underlying defects of expanded transitional or CD21low B cells remain to be elucidated. This trial is re-gistered at http://www.uniklinik-freiburg.de/zks/live/uklregister/Oeffentlich.html as UKF000308.

scholarly journals Mediastinal lymphoma of clear cell type is a tumor corresponding to terminal steps of B cell differentiation

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1087-1095 ◽  
Author(s):  
P Moller ◽  
G Moldenhauer ◽  
F Momburg ◽  
B Lammler ◽  
M Eberlein-Gonska ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cell ◽  
Clear Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
B Cell Differentiation ◽  
Mediastinal Tumors ◽  
Hla Dr ◽  
Mediastinal Lymphoma ◽  
Predominantly Female

Abstract This article reports eight primary mediastinal tumors occurring in young adults (19 to 43 years, mean 29.4 years), predominantly female (six of eight) adults. Most patients responded badly to aggressive therapy. Progression is presently noted in one patient; five patients died 10, 11, 13, 18, and 22 months after diagnosis. No patient developed leukemia. The tumors were highly proliferative, had a diffuse growth pattern, and comprised clear cells of variable size. They could not be classified histologically, but could, however, be immunohistologically characterized as B cell lymphomas. In all cases, the immunophenotype was LC+, cALLa-, CD19+, CD20+, CD21-, Ig (surface/cytoplasm)-, and PC-1+. In addition, the neoplastic cells exhibited variable defects in the expression of HLA-A,B,C and HLA-DR and inconstant expression of other B cell-restricted/associated antigens. This combination of immunophenotypical and clinical features suggests that the mediastinal clear cell lymphoma (MCCL) is a previously undescribed type of B cell lymphoma corresponding to the terminal steps of B cell differentiation.

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