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Identification of BCell Defects UsingAge-Defined ReferenceRanges for In Vivoand In Vitro B CellDifferentiation Daan J. aan de KerkMachiel H. JansenIneke J. M. ten Berge2013 год

Identification of B Cell Defects Using Age-Defined Reference Ranges for In Vivo and In Vitro B Cell Differentiation
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Аннотация: Primary immunodeficiencies consist to a large extent of B cell defects, as indicated by inadequate Ab levels or response upon immunization. Many B cell defects have not yet been well characterized. Our objective was to create reliable in vivo and in vitro assays to routinely analyze human B cell differentiation, proliferation, and Ig production and to define reference ranges for different age categories. The in vitro assays were applied to classify the developmental and/or functional B cell defects in patients previously diagnosed with common variable immunodeficiency. Apart from standard immunophenotyping of circulating human B cell subsets, an in vitro CFSE dilution assay was used for the assessment of proliferative capacity comparing T cell-dependent and T cell-independent B cell activation. Plasmablast/plasma cell differentiation was assessed by staining for CD20, CD38, and CD138, and measurement of in vitro Ig secretion. At young age, B cells proliferate upon in vitro activation, but neither differentiate nor produce IgG. These latter functions reached adult levels at 5 and 10 y of age for T cell-dependent versus T cell-independent stimulations, respectively. The capacity of B cells to differentiate into plasmablasts and to produce IgG appeared to be contained within the switched memory B cell pool. Using these assays, we could categorize common variable immunodeficiency patients into subgroups and identified a class-switch recombination defect caused by an UNG mutation in one of the patients. We defined age-related reference ranges for human B cell differentiation. Our findings indicate that in vivo B cell functionality can be tested in vitro and helps to diagnose suspected B cell defects.
Год издания: 2013
Авторы: Daan J. aan de Kerk, Machiel H. Jansen, Ineke J. M. ten Berge, Ester M. M. van Leeuwen, Taco W. Kuijpers
Издательство: American Association of Immunologists
Источник: The Journal of Immunology
Ключевые слова: Immunodeficiency and Autoimmune Disorders, T-cell and B-cell Immunology, Blood disorders and treatments
Другие ссылки: The Journal of Immunology (HTML)
PubMed (HTML)