Transcriptional analysis of the B cell germinal center reaction.
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.
Klein
Ulf
U
Institute for Cancer Genetics and Department of Pathology, Columbia University, New York, NY 10032, USA.
Tu
Yuhai
Y
Stolovitzky
Gustavo A
GA
Keller
Jeffrey L
JL
Haddad
Joseph
J
Miljkovic
Vladan
V
Cattoretti
Giorgio
G
Califano
Andrea
A
Dalla-Favera
Riccardo
R
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
C508020:IL2RB protein, human; D053646:Interleukin-2 Receptor beta Subunit; D016271:Proto-Oncogene Proteins c-myc; D018123:Receptors, Interleukin