Expression of apoptosis regulators in germinal centers and germinal center-derived B-cell lymphomas: Insight into B-cell lymphomagenesis

Germinal centers (GC) are unique sites in peripheral lymphoid tissue where clonal selection of B cells takes place in response to stimulation by various antigens. To select a proper B-cell clone for antibody-mediated immunity, multiple apoptotic signals synchronize in the GC, both in negative and positive selection pathways. At the same time, GC have been known to be a major source of B-cell lymphomas including follicular and Burkitt's, and also some diffuse large B-cell lymphomas. Therefore, uncovering the biological characteristics of GC would greatly contribute to understanding lymphomagenesis, or progression of B-cell lymphomas of GC origin. Herein the authors briefly explain the expression and pathophysiological significance of apoptosis regulators in GC, focusing particularly on Bcl-2, Fas (CD95) and a transcription factor, nuclear factor of activated T cells, which seems to play a critical role in regulating cellular dynamics of GC B cells via B-cell antigen receptor. The expression of these molecules is then compared with that of the neoplastic counterpart B-cell lymphomas in order to consider lymphomagenesis of GC origin. In conclusion, follicular lymphoma closely reflected characteristics of GC among these B-cell lymphomas, although it acquires strong expression of apoptosis-resistant gene, bcl-2.