کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6066107 1201882 2014 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Immune deficiencies, infection, and systemic immune disordersThe BLNK adaptor protein has a nonredundant role in human B-cell differentiation
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Immune deficiencies, infection, and systemic immune disordersThe BLNK adaptor protein has a nonredundant role in human B-cell differentiation
چکیده انگلیسی

BackgroundExpression of the pre-B-cell receptor (pre-BCR) by pre-BII cells constitutes a crucial checkpoint in B-cell differentiation. Mutations that affect the pre-B-cell receptor result in early B-cell differentiation blockades that lead to primary B-cell immunodeficiencies. BLNK adaptor protein has a key role in the pre-B-cell receptor signaling cascade, as illustrated by the abnormal B-cell development in the 4 patients with BLNK gene defects reported to date. However, the BLNK protein's precise function in human B-cell differentiation has not been completely specified.MethodsB-cell development, including IgVH and Vk chain repertoires analysis, was studied in the bone marrow of a new case of BLNK deficiency in vitro and in vivo.ResultsHere, we report on a patient with agammaglobulinemia, with a total absence of circulating B cells. We detected a homozygous mutation in BLNK, which leads to the complete abrogation of BLNK protein expression. In the bone marrow, we identified a severe differentiation blockade at the pre-BI- to pre-BII-cell transition. IgVH gene rearrangements and selection of the IgH repertoire were normal, whereas the patient's pre-BI cells showed very restricted usage of the IgVκ repertoire. Complementation of bone marrow progenitors from the patient with the BLNK gene and transplantation into NOD/SCID/γcko mice allowed the complete restoration of B-cell differentiation and a normal usage of the IgVκ genes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Allergy and Clinical Immunology - Volume 134, Issue 1, July 2014, Pages 145-154.e3
نویسندگان
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