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Replacing mouse BAFF with human BAFF does not improve B-cell maturation in hematopoietic humanized mice.
Lang, Julie; Zhang, Bicheng; Kelly, Margot; Peterson, Jacob N; Barbee, Jacob; Freed, Brian M; Di Santo, James P; Matsuda, Jennifer L; Torres, Raul M; Pelanda, Roberta.
Afiliação
  • Lang J; Department of Immunology and Microbiology, School of Medicine, University of Colorado Denver, Aurora, CO.
  • Zhang B; Department of Biomedical Research, National Jewish Health, Denver, CO.
  • Kelly M; Department of Immunology and Microbiology, School of Medicine, University of Colorado Denver, Aurora, CO.
  • Peterson JN; Department of Immunology and Microbiology, School of Medicine, University of Colorado Denver, Aurora, CO.
  • Barbee J; Department of Immunology and Microbiology, School of Medicine, University of Colorado Denver, Aurora, CO.
  • Freed BM; Division of Allergy and Clinical Immunology, School of Medicine, University of Colorado Denver, Aurora, CO.
  • Di Santo JP; Innate Immunity Unit, Institut Pasteur, Paris, France; and.
  • Matsuda JL; U1223, INSERM, Paris, France.
  • Torres RM; Department of Biomedical Research, National Jewish Health, Denver, CO.
  • Pelanda R; Department of Immunology and Microbiology, School of Medicine, University of Colorado Denver, Aurora, CO.
Blood Adv ; 1(27): 2729-2741, 2017 Dec 26.
Article em En | MEDLINE | ID: mdl-29296925
Hematopoietic humanized mice (hu-mice) have been developed to study the human immune system in an experimental in vivo model, and experiments to improve its performance are ongoing. Previous studies have suggested that the impaired maturation of human B cells observed in hu-mice might be in part due to inefficient interaction of the human B-cell-activating factor (hBAFF) receptor with mouse B-cell-activating factor (mBAFF), as this cytokine is an important homeostatic and differentiation factor for B lymphocytes both in mice and humans. To investigate this hypothesis, we created a genetically engineered mouse strain in which a complementary DNA (cDNA) encoding full-length hBAFF replaces the mBAFF-encoding gene. Expression of hBAFF in the endogenous mouse locus did not lead to higher numbers of mature and effector human B cells in hu-mice. Instead, B cells from hBAFF knock-in (hBAFFKI) hu-mice were in proportion more immature than those of hu-mice expressing mBAFF. Memory B cells, plasmablasts, and plasma cells were also significantly reduced, a phenotype that associated with diminished levels of immunoglobulin G and T-cell-independent antibody responses. Although the reasons for these findings are still unclear, our data suggest that the inefficient B-cell maturation in hu-mice is not due to suboptimal bioactivity of mBAFF on human B cells.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Blood Adv Ano de publicação: 2017 Tipo de documento: Article País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Blood Adv Ano de publicação: 2017 Tipo de documento: Article País de publicação: Estados Unidos