title: Biphenotypic B-lymphoid/myeloid cells expressing low levels of Pax5: potential targets of BAL development.
abstract: The expression of Pax5 commits common lymphoid progenitor cells to B-lymphoid lineage differentiation. Little is known of possible variations in the levels of Pax5 expression and their influences on hematopoietic development. We have developed a retroviral transduction system that allows for the study of possible intermediate stages of this commitment by controlling the levels of Pax5 expressed in Pax5-deficient progenitors in vitro and in vivo. Retroviral transduction of Pax5-deficient pro-/pre-B cell lines with a doxycycline-inducible (TetON) form of the human Pax5 (huPax5) gene yielded cell clones that could be induced to different levels of huPax5 expression. Clones inducible to high levels developed B220(+)/CD19(+)/IgM(+) B cells, while clones with low levels differentiated to B220(+)/CD19(-)/CD11b(+)/Gr-1(-) B-lymphoid/myeloid biphenotypic cells in vitro and in vivo. Microarray analyses of genes expressed at these lower levels of huPax5 identified C/ebpα, C/ebpδ, Pu.1, Csf1r, Csf2r, and Gata-3 as myeloid-related genes selectively expressed in the pro-/pre-B cells that can develop under myeloid/lymphoid conditions to biphenotypic cells. Therefore, reduced expression of huPax5 during the induction of early lymphoid progenitors to B-lineage-committed cells can fix this cellular development at a stage that has previously been seen during embryonic development and in acute lymphoblastic lymphoma-like biphenotypic acute leukemias.
authors.affiliation: Lymphocyte Development Group, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Szandor
authors.initials: S
authors.lastname: Simmons
authors.forename: Marko
authors.initials: M
authors.lastname: Knoll
authors.forename: Christopher
authors.initials: C
authors.lastname: Drewell
authors.forename: Ingrid
authors.initials: I
authors.lastname: Wolf
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Mollenkopf
authors.forename: Corinne
authors.initials: C
authors.lastname: Bouquet
authors.forename: Fritz
authors.initials: F
authors.lastname: Melchers
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051757:PAX5 Transcription Factor / Q000378:metabolism*; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism* / Q000473:pathology; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014161:Transduction, Genetic
chemical_list: D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human