title: PAX5 promotes pre-B cell proliferation by regulating the expression of pre-B cell receptor and its downstream signaling.
abstract: PAX5 is indispensable for the commitment of early lymphoid progenitors to the B cell lineage as well as for the development of B cells. Although previous studies have indicated that the Pax5-conditional-knockout mouse exhibited dedifferentiation of mature B cell and the development of aggressive lymphomas, the changes of Pax5 gene expressions in pre-B cells have not been analyzed. To understand the functional importance of Pax5 gene in the proliferation and survival of pre-B cells, we established a Pax5-knockdown model using 70Z/3 pre-B cell line. Pax5 knockdown 70Z/3 cells (70Z/3-KD cells) showed down-regulations of pre-BCR compounds such as CD19, BLNK, Id2 and λ5. The signaling via pre-BCRs was significantly diminished in the 70Z/3-KD cells, and this alteration was normalized by restored Pax5 gene expression. Loss of PAX5 reduced the growth rates in the 70Z/3-KD cells, compared to the mock cells. Meanwhile, the proliferation of pre-B cells was reduced by the knockdown of Pax5 gene. Moreover, further examinations showed that PAX5 was also activated in B cell acute lymphoblastic leukemia (B-ALL) as a cell proliferation enhancer. These findings suggested that pax5 is critically important for the proliferation and survival of pre-B cells.
authors.affiliation: College of Basic Medical Sciences, Dalian Medical University, 9-Western Section, Lvshun South Road, Dalian, Liaoning 116044, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Xue
authors.affiliation: College of Basic Medical Sciences, Dalian Medical University, 9-Western Section, Lvshun South Road, Dalian, Liaoning 116044, China.
authors.forename: Jiazhe
authors.initials: J
authors.lastname: Song
authors.affiliation: College of Basic Medical Sciences, Dalian Medical University, 9-Western Section, Lvshun South Road, Dalian, Liaoning 116044, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Clinical Laboratory, Dalian Municipal Central Hospital, 826-Xinan Road, Shahekou District, Dalian city, Liaoning 116003, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Dalian Academy of Agricultural Sciences, Dalian, Liaoning 116036, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Wu
authors.affiliation: College of Basic Medical Sciences, Dalian Medical University, 9-Western Section, Lvshun South Road, Dalian, Liaoning 116044, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Jin
authors.affiliation: College of Basic Medical Sciences, Dalian Medical University, 9-Western Section, Lvshun South Road, Dalian, Liaoning 116044, China. Electronic address: liwenzhe46@hotmail.com.
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Li
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D002469:Cell Separation; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D055785:Gene Knockdown Techniques; D006801:Humans; D016393:Lymphoma, B-Cell / Q000276:immunology; D051757:PAX5 Transcription Factor / Q000276:immunology* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D054420:Pre-B Cell Receptors / Q000096:biosynthesis* / Q000276:immunology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D051757:PAX5 Transcription Factor; D054420:Pre-B Cell Receptors
keywords: B cell development; Cell proliferation; PAX5; Pre-BCR signaling