title: Transcriptional analysis of the B cell germinal center reaction.
abstract: The germinal center (GC) reaction is crucial for T cell-dependent immune responses and is targeted by B cell lymphomagenesis. Here we analyzed the transcriptional changes that occur in B cells during GC transit (naive B cells --> centroblasts --> centrocytes --> memory B cells) by gene expression profiling. Naive B cells, characterized by the expression of cell cycle-inhibitory and antiapoptotic genes, become centroblasts by inducing an atypical proliferation program lacking c-Myc expression, switching to a proapoptotic program, and down-regulating cytokine, chemokine, and adhesion receptors. The transition from GC to memory cells is characterized by a return to a phenotype similar to that of naive cells except for an apoptotic program primed for both death and survival and for changes in the expression of cell surface receptors including IL-2 receptor beta. These results provide insights into the dynamics of the GC reaction and represent the basis for the analysis of B cell malignancies.
authors.affiliation: Institute for Cancer Genetics and Department of Pathology, Columbia University, New York, NY 10032, USA.
authors.forename: Ulf
authors.initials: U
authors.lastname: Klein
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Tu
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Stolovitzky
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Keller
authors.forename: Joseph
authors.initials: J
authors.lastname: Haddad
authors.forename: Vladan
authors.initials: V
authors.lastname: Miljkovic
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cattoretti
authors.forename: Andrea
authors.initials: A
authors.lastname: Califano
authors.forename: Riccardo
authors.initials: R
authors.lastname: Dalla-Favera
mesh_terms: D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002448:Cell Adhesion; D002455:Cell Division; D002469:Cell Separation; D015536:Down-Regulation; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D018858:Germinal Center; D006801:Humans; D007150:Immunohistochemistry; D007156:Immunologic Memory; D053646:Interleukin-2 Receptor beta Subunit; D008280:Magnetics; D020411:Oligonucleotide Array Sequence Analysis; D014066:Palatine Tonsil / Q000166:cytology; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D018123:Receptors, Interleukin / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: C508020:IL2RB protein, human; D053646:Interleukin-2 Receptor beta Subunit; D016271:Proto-Oncogene Proteins c-myc; D018123:Receptors, Interleukin