Hypomorphic <i>Rag1</i> mutations alter the preimmune repertoire at early stages of lymphoid development.

ABSTRACT: Hypomorphic RAG1 mutations allowing residual T- and B-cell development have been found in patients presenting with delayed-onset combined immune deficiency with granulomas and/or autoimmunity (CID-G/AI) and abnormalities of the peripheral T- and B-cell repertoire. To examine how hypomorphic Rag1 mutations affect the earliest stages of lymphocyte development, we used CRISPR/Cas9 to generate mouse models with mutations equivalent to those found in patients with CID-G/AI. Immunological characterization showed partial development of T and B lymphocytes, with persistence of naïve cells and preserved serum immunoglobulin but impaired antibody responses and presence of autoantibodies, thereby recapitulating the phenotype seen in patients with CID-G/AI. By using high-throughput seque

SUBMITTER: Ott de Bruin LM 

PROVIDER: S-EPMC6053949 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature