MHV68 Infection in a Novel rag2 F62L/F62L Mouse Model Based on a Patient with CID-G/AI Phenotype
Poster Feb 27, 2017
Csomos K, Ujhazi B, Stoltz K, Ijspeert H, Mei Yan, Quan-Zhen Li, Csizmadia E, Butte MJ, Coppola D, van der Burg M, Tarakanova V, Walter JE
Objective: Immunodeficiencies secondary to partial RAG1/2 mutations have a widening autoimmune clinical spectrum and autoantibodies, including those targeting cytokines. Herpes virus infections are often observed prior to the onset of autoimmunity.
Methods: To study this phenomenon, a novel murine model was designed with rag2F62L/F62L (mut/mut) modeling a patient with partial Rag deficiency (19.6% Rag2 recombinase activity), history of autoimmune cytopenia and complicated herpes virus infection. Mice were infected with mouse gammaherpesvirus-68 (MHV-68) and cellular and humoral response were monitored. B cell tolerance checkpoints were examined.
Results: At baseline mut/mut mice had increased use of proximal IgH J genes consistent with partial Rag activity. Although viral latency was comparable, antibody generation to virus and self-antigens were increased and larger lymphoid infiltrates (lung, liver, kidney) were noted in mut/mut versus wt/wt mice (p<0.05). Receptor editing in bone marrow Fraction D B cells, serum B cell activating factor (BAFF) levels and regulatory T compartments did not differ significantly.
Conclusions: MHV-68 infection in our rag2 mouse model induced increased antibody responses to virus and self and inflammatory disease in end organs. Major mechanism of inflammatory infiltrates and autoantibody generation is yet to be determined
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