title: Differential induction of DNA-binding activities following CD19 cross-linking in human B lineage cells.
abstract: The B cell-specific cell surface molecule CD19 is expressed at all stages of B cell development, including normal plasma cells, and mediates signal transduction via interaction with cytoplasmic effector proteins. Cross-linking CD19 on early human B lineage cells induces the formation of a CD19/Vav/phosphatidylinositol-3 kinase complex, tyrosine phosphorylation of CD19 and Vav, and activation of the Ras pathway. To further explore the ramifications of CD19 signaling, the current study examined whether phosphorylation of Elk-1, activation of activator protein-1 (AP-1), or activation of nuclear factor-kappaB (NF-kappaB) transcription factors occurred following CD19 cross-linking. The cells used were the BLIN-1 pre-B cell line expressing low levels of cell surface mu heavy chain associated with surrogate light chain and the 1E8 immature B cell line expressing cell surface mu/kappa. Lysates from CD19 cross-linked 1E8 cells induced robust phosphorylation of an Elk-1 fusion protein in vitro, whereas no phosphorylation of Elk-1 fusion protein occurred using lysates from CD19 cross-linked BLIN-1 cells. An electrophoretic mobility shift assay employing AP-1 and NF-kappaB consensus oligonucleotides was used to demonstrate that AP-1 -binding activity increased, while constitutive NF-kappaB-binding activity was not enhanced, following 2 h of CD19 cross-linking in 1E8 cells. Supershift experiments revealed that JunD and c-Fos proteins mediated anti-CD19 induced AP-1-binding activity in 1E8 cells. In contrast, CD19 cross-linking in BLIN-1 cells resulted in the induction of NF-kappaB, but had no apparent effect on AP-1-binding activity. These data suggest that CD19-mediated signal transduction activates different transcription factors at juxtaposed stages of B cell development that may culminate in the activation or suppression of distinct sets of genes.
authors.affiliation: Department of Laboratory Medicine/Pathology, University of Minnesota Medical School, Minneapolis 55455, USA.
authors.forename: W K
authors.initials: WK
authors.lastname: Weng
authors.forename: N
authors.initials: N
authors.lastname: Shah
authors.forename: D
authors.initials: D
authors.lastname: O'Brien
authors.forename: B
authors.initials: B
authors.lastname: Van Ness
authors.forename: T W
authors.initials: TW
authors.lastname: LeBien
mesh_terms: D018941:Antigens, CD19 / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism*; D004268:DNA-Binding Proteins; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D050807:ets-Domain Protein Elk-1
chemical_list: D018941:Antigens, CD19; D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1