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Generation of precursor, immature, and mature murine B1-cell lines from c-myc/bcl-xL-overexpressing pre-BI cells.
Wolf, Inge; Bouquet, Corinne; Naumann, Friederike; Melchers, Fritz.
Afiliação
  • Wolf I; Max Planck Institute for Infection Biology, Berlin, Germany.
  • Bouquet C; Max Planck Institute for Infection Biology, Berlin, Germany.
  • Naumann F; Max Planck Institute for Infection Biology, Berlin, Germany.
  • Melchers F; Max Planck Institute for Infection Biology, Berlin, Germany.
Eur J Immunol ; 47(5): 911-920, 2017 05.
Article em En | MEDLINE | ID: mdl-28294314
ABSTRACT
Deregulated expression of c-myc and bcl-xL is long known to generate transformed B cells in humans and mice. We overexpressed these genes to induce in vitro and in vivo differentiation of fetal liver-derived mouse pre-BI cells to B1-lineage pre-BII-like, immature and mature B-cell lines, and to Ig-secreting cells. In vitro, doxycycline-controlled c-myc/bcl-xL-overexpressing CD19+ CD93+ c-kikt+ IgM- pre-BI cells differentiate to and survive as CD19+ CD93+ c-kit- IgM+ immature B1 cells. Timed CpG stimulation of these oncogene-overexpressing pre-B or immature B1 cells generates either CD19+ CD93low c-kit- IgM- SLC- pre-BII-like or IgM+ MHCII+ CD73+ CD80+ CD40+ mature B1-cell lines and IgM-secreting B1 cells in vitro and fixes their state of differentiation. All cell lines are clonable, but a majority of immature and mature B1-cell clones eventually reach a nonproliferating, surviving G0 -state. Transplanted in vivo, c-myc/bcl-xL-overexpressing pre-B cells expand to mature B1 cells, and to IgM- and IgA-secreting plasmablasts and plasma cells. Within 2 months, plasmablasts have expanded most prominently in BM and spleen, indicating that the host selectively expanded development of these transformed plasma cells. The sIgM+ B1-cell lines and clones offer the possibility to study their roles in the development of B1-Ab repertoires, of B1-cell-mediated autoimmune diseases and of B1-cell malignancies.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos B / Células Precursoras de Linfócitos B Idioma: En Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos B / Células Precursoras de Linfócitos B Idioma: En Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Alemanha