title: Generation of precursor, immature, and mature murine B1-cell lines from c-myc/bcl-xL-overexpressing pre-BI cells.
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+CD93lowc-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.
authors.affiliation: Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Inge
authors.initials: I
authors.lastname: Wolf
authors.affiliation: Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Corinne
authors.initials: C
authors.lastname: Bouquet
authors.affiliation: Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Naumann
authors.affiliation: Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Fritz
authors.initials: F
authors.lastname: Melchers
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002454:Cell Differentiation; D002460:Cell Line; D016259:Genes, myc; D007070:Immunoglobulin A / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology; D051379:Mice; D010950:Plasma Cells / Q000276:immunology / Q000502:physiology; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494812:Bcl2l1 protein, mouse; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D051020:bcl-X Protein; C033027:secretory IgM
keywords: B1-cell differentiation; CpG stimulation; Pre-BI cell; Proliferation; c-myc/bcl-xL