ThePromoter oftheCD19GeneIsa Target fortheB-Cell-Specific Transcription Factor BSAP

receptor inthecontrol of proliferation anddifferentiation. Herewe demonstrate complete correlation between theexpression pattern of theCD19geneandtheB-cell-specific transcription factor BSAPinalarge panel ofB-lymphoid cell lines. The humanCD19genehasbeencloned, andseveral BSAP-binding sites havebeenmappedbyinvitro protein-DNA binding studies. Inparticular, a high-affinity BSAP-binding site instead ofa TATA sequenceislocated inthe -30promoter region upstream ofa cluster ofheterogeneous transcription start sites. Moreover, this site is occupied byBSAPinvivoina CD19-expressing B-cell line butnotinplasma orHeLacells. Thishigh-affinity site hasbeenconserved inthepromoters ofbothhumanandmouse CD19genesandwas furthermore shown toconfer B-cell specificity toaf-globin reporter geneintransient transfection experiments. Inaddition, BSAP was found tobetheonlyabundant DNA-binding activity ofB-cell nuclear extracts thatinteracts withtheCD19 promoter. Together, this evidence strongly implicates BSAPintheregulation oftheCD19gene. Thedifferentiation ofBlymphocytes fromprogenitor cells toimmunoglobulin-secreting plasmacellsisa multistep processwhichischaracterized bythesequential expression ofspecific cell surface markers involved incell-cell interac- tionandsignal transduction (29). AmongthemistheB-cell- specific antigen CD19.Thisprotein isexpressed throughout B-cell ontogenyfromtheearly progenitor cell up tothe matureB-cell stageandislost fromthecell surface onlyat theterminal stagesofB-cell differentiation. TheCD19mol- eculeispresent on bothnormalandmalignant B-lymphoid cells andhenceisthemostreliable diagnostic surface marker ofthehumanB-cell lineage (23, 35). TheCD19gene codes