Back to Search
Start Over
Characterization of T and B cell repertoire diversity in patients with RAG deficiency.
- Source :
-
Science immunology [Sci Immunol] 2016 Dec 16; Vol. 1 (6). Date of Electronic Publication: 2016 Dec 16. - Publication Year :
- 2016
-
Abstract
- Recombination-activating genes 1 and 2 ( RAG1 and RAG2 ) play a critical role in T and B cell development by initiating the recombination process that controls the expression of T cell receptor (TCR) and immunoglobulin genes. Mutations in the RAG1 and RAG2 genes in humans cause a broad spectrum of phenotypes, including severe combined immunodeficiency (SCID) with lack of T and B cells, Omenn syndrome, leaky SCID, and combined immunodeficiency with granulomas or autoimmunity (CID-G/AI). Using next-generation sequencing, we analyzed the TCR and B cell receptor (BCR) repertoire in 12 patients with RAG mutations presenting with Omenn syndrome ( n = 5), leaky SCID ( n = 3), or CID-G/AI ( n = 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.<br /> (Copyright © 2016, American Association for the Advancement of Science.)
Details
- Language :
- English
- ISSN :
- 2470-9468
- Volume :
- 1
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Science immunology
- Publication Type :
- Academic Journal
- Accession number :
- 28783691
- Full Text :
- https://doi.org/10.1126/sciimmunol.aah6109