Transcriptional analysis of the B cell germinal center reaction

TLDR

The germinal center reaction is essential for T cell‑dependent immune responses and is a target of B cell lymphomagenesis. The study analyzes transcriptional changes in B cells during germinal center transit from naïve to centroblasts, centrocytes, and memory cells. This analysis was performed using gene expression profiling. Naïve B cells express cell cycle‑inhibitory and anti‑apoptotic genes, then become centroblasts with an atypical proliferation program lacking c‑Myc, switch to a pro‑apoptotic program, and down‑regulate cytokine, chemokine, and adhesion receptors, while the GC‑to‑memory transition restores a naive‑like phenotype but primes an apoptotic program and alters surface receptor expression such as IL‑2Rβ, providing insights into GC dynamics and a basis for studying B‑cell malignancies.

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 (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.