Transcriptional analysis of the B cell germinal center reaction

U Klein, Y Tu, GA Stolovitzky… - Proceedings of the …, 2003 - National Acad Sciences
U Klein, Y Tu, GA Stolovitzky, JL Keller, J Haddad Jr, V Miljkovic, G Cattoretti, A Califano
Proceedings of the National Academy of Sciences, 2003National Acad Sciences
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 (naïve B cells→ centroblasts→ centrocytes→ memory B
cells) by gene expression profiling. Naïve 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 …
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 (naïve B cells → centroblasts → centrocytes → memory B cells) by gene expression profiling. Naïve 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 naïve 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 β. These results provide insights into the dynamics of the GC reaction and represent the basis for the analysis of B cell malignancies.
National Acad Sciences