Bcl-6 Uncouples B Lymphocyte Proliferation from Differentiation
The effective stimulation of lymphocytes by antigen has three potential outcomes for antigen-specific clones, their replication leading to net expansion of cell numbers, their differentiation into effector cells and their differentiation into memory cells. The coordination of these cellular responses is important because, as in other cellular systems, differentiation to the effector stage of development may be associated with an inability to replicate further. For B lymphocytes, terminal differentiation is coupled to cessation of mitosis since non-transformed plasma cells cannot re-enter the cell cycle; it is not clear if terminally differentiated effector T cells have a similar limitation. Therefore, in the immune sytem where the number of antigen-specific clones in a naïve individual is low, premature terminal differentiation occurring before sufficient cellular replication has been achieved would limit the effectiveness of an immune response. Yet, the need for clonal expansion must be appropriately balanced with the obvious benefits of early control and elimination of the infectious process by differentiated lymphocytes. Finally, control of effector cell differentiation and function in the immune system may protect the individual from autoimmune or allergic disease.
KeywordsZinc Lymphoma Estrogen Leukemia Germinal
Unable to display preview. Download preview PDF.
- 8.B.W. Baron, G. Nucifora, N. McCabe, R. Espinosa III, M.M. Le Beau, and T.W. McKeithan, 1993, Identification of the gene associated with the recurring chromosomal translocations t(3;14)(q27;q32) and t(3;22)(g27;g11) in B-cell lymphomasProc. Natl. Acad. Sci. USA 90,5262–5266.CrossRefPubMedPubMedCentralGoogle Scholar
- 17.K.F. Ahmad, C.K. Engel, and G.G. Prive GG, 1998, Crystal structure of the BTB domain from PLZFProc. Natl. Acad. Sci. USA 95,121231212–8Google Scholar
- 26.M.B. Harris, C.C. Chang, M.T. Berton, N.N. Danial, J. Zhang, D. Kuehner, B.H. Ye, M. Kvatyuk, P.P. Pandolfi, G. Cattoretti, R. Dalla-Favera, and P.B. Rothman, 1999, Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: specific regulation of iepsilon transcription and immunoglobulin E switchingMol. Cell Biol.19, 7264–7275.CrossRefGoogle Scholar
- 33.B.H. Ye, G. Cattoretti, Q. Shen, J. Zhang, N. Hawe, R. de Waard, C. Leung, M. NouriShirazi, A. Orazi, R.S. Chaganti, P. Rothman, A.M. Stall, P.P. Pandolfi, and R. Dalla-Favera, 1997, The BCL-6 proto-oncogene controls germinal-centre formation and Th2-type inflammationNat. Genet. 16,161–170.CrossRefPubMedGoogle Scholar
- 38.M.A. Blackman, M.A.TiggeS, M.E. Minie, and M.E. Koshland, 1986, A model system for peptide hormone action in differentiation: interleukin 2 induces a B lymphoma to transcribe the J chain geneCell 47,609–617.Google Scholar