Characterization of T and B cell repertoire diversity in patients with RAG deficiency

作者：Yu Nee Lee, Francesco Frugoni, Kerry Dobbs, Irit Tirosh, Likun Du, Francesca A. Ververs, Heng Ru, Lisa Ott de Bruin, Mehdi Adeli, Jacob H. Bleesing, David Buchbinder, Manish J. Butte, Caterina Cancrini, Karin Chen, Sharon Choo, Reem Elfeky, Andrea Finocchi, Ramsay Fuleihan, Andrew R. Gennery, Dalia El‐Ghoneimy, Lauren A. Henderson, Waleed Al–Herz, Elham Hossny, Robert P. Nelson, Sung‐Yun Pai, Niraj Patel, Shereen M. Reda, Pere Soler‐Palacín, Raz Somech, Paolo Palma, Hao Wu, Silvia Giliani, Jolán E. Walter, Luigi D. Notarangelo · 发表于：Science Immunology · 年份：2016 · DOI：10.1126/sciimmunol.aah6109 · 被引用次数：117 · 研究领域：Immunodeficiency and Autoimmune Disorders、Cystic Fibrosis Research Advances、Genetics and Neurodevelopmental Disorders

= 4). Restriction of repertoire diversity skewed usage of variable (V), diversity (D), and joining (J) segment genes, and abnormalities of CDR3 length distribution were progressively more prominent in patients with a more severe phenotype. Skewed usage of V, D, and J segment genes was present also within unique sequences, indicating a primary restriction of repertoire. Patients with Omenn syndrome had a high proportion of class-switched immunoglobulin heavy chain transcripts and increased somatic hypermutation rate, suggesting in vivo activation of these B cells. These data provide a framework to better understand the phenotypic heterogeneity of RAG deficiency.