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MYSM1-dependent checkpoints in B cell lineage differentiation and B cell-mediated immune response.
Förster, Michael; Farrington, Kyo; Petrov, Jessica C; Belle, Jad I; Mindt, Barbara C; Witalis, Mariko; Duerr, Claudia U; Fritz, Jörg H; Nijnik, Anastasia.
Afiliación
  • Förster M; Department of Physiology, McGill University, Montreal, Quebec, Canada.
  • Farrington K; McGill University Research Centre on Complex Traits, Montreal, Quebec, Canada; and.
  • Petrov JC; Department of Physiology, McGill University, Montreal, Quebec, Canada.
  • Belle JI; McGill University Research Centre on Complex Traits, Montreal, Quebec, Canada; and.
  • Mindt BC; Department of Physiology, McGill University, Montreal, Quebec, Canada.
  • Witalis M; McGill University Research Centre on Complex Traits, Montreal, Quebec, Canada; and.
  • Duerr CU; Department of Physiology, McGill University, Montreal, Quebec, Canada.
  • Fritz JH; McGill University Research Centre on Complex Traits, Montreal, Quebec, Canada; and.
  • Nijnik A; McGill University Research Centre on Complex Traits, Montreal, Quebec, Canada; and.
J Leukoc Biol ; 101(3): 643-654, 2017 03.
Article en En | MEDLINE | ID: mdl-27895164
MYSM1 is a chromatin-binding histone deubiquitinase. MYSM1 mutations in humans result in lymphopenia whereas loss of Mysm1 in mice causes severe hematopoietic abnormalities, including an early arrest in B cell development. However, it remains unknown whether MYSM1 is required at later checkpoints in B cell development or for B cell-mediated immune responses. We analyzed conditional mouse models Mysm1fl/flTg.mb1-cre, Mysm1fl/flTg.CD19-cre, and Mysm1fl/flTg.CD21-cre with inactivation of Mysm1 at prepro-B, pre-B, and follicular B cell stages of development. We show that loss of Mysm1 at the prepro-B cell stage in Mysm1fl/flTg.mb1-cre mice results in impaired B cell differentiation, with an ∼2-fold reduction in B cell numbers in the lymphoid organs. Mysm1fl/flTg.mb1-cre B cells also showed increased expression of activation markers and impaired survival and proliferation. In contrast, Mysm1 was largely dispensable from the pre-B cell stage onward, with Mysm1fl/flTg.CD19-cre and Mysm1fl/flTg.CD21-cre mice showing no alterations in B cell numbers and largely normal responses to stimulation. MYSM1, therefore, has an essential role in B cell lineage specification but is dispensable at later stages of development. Importantly, MYSM1 activity at the prepro-B cell stage of development is important for the normal programming of B cell responses to stimulation once they complete their maturation process.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Endopeptidasas / Linfocitos B / Diferenciación Celular / Linaje de la Célula / Puntos de Control del Ciclo Celular / Inmunidad Celular Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Leukoc Biol Año: 2017 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Endopeptidasas / Linfocitos B / Diferenciación Celular / Linaje de la Célula / Puntos de Control del Ciclo Celular / Inmunidad Celular Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Leukoc Biol Año: 2017 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido