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.
Kondo
Eisaku
E
Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. ekondo@md.okayama-u.ac.jp
Yoshino
Tadashi
T
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D018858:Germinal Center / Q000378:metabolism*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; D019014:fas Receptor