DIFFERENTIAL INDUCTION OF DNA-BINDING ACTIVITIES FOLLOWING CD19 CROSS-LINKING IN HUMAN B-LINEAGE CELLS

The B cell-specific fell surface molecule CD19 is expressed at all sta ges of B cell development, including normal plasma cells, and mediates signal transduction via interaction with cytoplasmic effector protein s, Cross-linking CD19 an early human B lineage cells induces the forma tion of a CD19/Vav/phosphatidylinositol-3 kinase complex, tyrosine pho sphorylation of CD19 and Vav, and activation of the Ras pathway. To fu rther explore the ramifications of CD19 signaling, the current study e xamined whether phosphorylation of Elk-1, activation of activator prot ein-1 (AP-1), or activation of nuclear factor-kappa B (NF-kappa B) tra nscription factors occurred following CD19 cross-linking, The cells us ed were the BLIN-1 pre-B cell line expressing low levels of cell surfa ce mu heavy chain associated with surrogate light chain and the 1E8 im mature B cell line expressing cell surface mu/kappa. Lysates from CD19 cross-linked 1E8 cells induced robust phosphorylation of an Elk-1 fus ion protein in vitro, whereas no phosphorylation of Elk-1 fusion prote in occurred using lysates from CD19 cross-linked BLIN-1 cells, An elec trophoretic mobility shift assay employing AP-1 and NF-kappa B consens us oligonucleotides was used to demonstrate that AP-1-binding activity increased, while constitutive NF-kappa B-binding activity was not enh anced, following 2 h of CD19 cross-linking in 1E8 cells, Supershift ex periments revealed that JunD and c-Fos proteins mediated anti-CD19 ind uced AP-1-binding activity in 1E8 cells, in contrast, CD19 cross-linki ng in BLIN-1 cells resulted in the induction of NF-kappa B, but had no apparent effect an AP-1-binding activity, These data suggest that CD1 9-mediated signal transduction activates different transcription facto rs at juxtaposed stages of B cell development that may culminate in th e activation or suppression of distinct sets of genes.