title: Repression of BCL-6 is required for the formation of human memory B cells in vitro.
abstract: Memory B cells provide rapid protection to previously encountered antigens; however, how these cells develop from germinal center B cells is not well understood. A previously described in vitro culture system using human tonsillar germinal center B cells was used to study the transcriptional changes that occur during differentiation of human memory B cells. Kinetic studies monitoring the expression levels of several known late B cell transcription factors revealed that BCL-6 is not expressed in memory B cells generated in vitro, and gene expression profiling studies confirmed that BCL-6 is not expressed in these memory B cells. Furthermore, ectopic expression of BCL-6 in human B cell cultures resulted in formation of fewer memory B cells. In addition, the expression profile of in vitro memory B cells showed a unique pattern that includes expression of genes encoding multiple costimulatory molecules and cytokine receptors, antiapoptotic proteins, T cell chemokines, and transcription factors. These studies establish new molecular criteria for defining the memory B cell stage in human B cells.
authors.affiliation: Department of Microbiology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Tracy C
authors.initials: TC
authors.lastname: Kuo
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Shaffer
authors.forename: Joseph
authors.initials: J
authors.lastname: Haddad
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Choi
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.forename: Kathryn
authors.initials: K
authors.lastname: Calame
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007700:Kinetics; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger; D004247:DNA