Suppression of Signal Transducer and Activator of Transcription 3-Dependent B Lymphocyte Terminal Differentiation by Bcl-6

doi:10.1084/jem.192.12.1841

Published online 18 December 2000.

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© The Rockefeller University Press, 0022-1007/2000/12/1841/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 12, December 18, 2000 1841-1848

Brief Definitive Report

Suppression of Signal Transducer and Activator of Transcription 3–Dependent B Lymphocyte Terminal Differentiation by Bcl-6

Rajko Reljic^a, Simon D. Wagner^a^,b, Luke J. Peakman^a, and Douglas T. Fearon^a

^a Wellcome Trust Immunology Unit, University of Cambridge, School of Clinical Medicine, Cambridge CB2 2SP, United Kingdom
^b Department of Haematology, Addenbrookes Hospital, Cambridge CB2 2SP, United Kingdom
Wellcome Trust Immunology Unit, MRC Centre, Hills Road, Cambridge CB2 2SP, UK.44-1223-33681744-1223-330528

dtf1000{at}cus.cam.ac.uk

Lymphocytes usually differentiate into effector cells withindays after antigen exposure, except in germinal centers whereterminal differentiation is delayed while somatic hypermutationcreates high-affinity antibody mutants. Here we investigatewhether arrest of terminal differentiation can be mediated byBCL-6, a transcriptional repressor that is expressed by germinalcenter B cells and is required for this phase of B cell development.We find that BCL-6 suppresses the differentiation of transformedand primary B cells to plasma cells by inhibiting the signaltransducer and activator of transcription 3–dependentexpression of the major regulator of plasma cell development,the B lymphocyte–induced maturation protein (Blimp-1).This function of BCL-6 as a repressor of B lymphocyte differentiationmay also underlie the association between chromosomal translocationsof its gene and B cell lymphomas.

Key Words: BTB-POZ protein • plasma cell • germinal center • retrovirus • interleukins

R. Reljic and S.D. Wagner contributed equally to this work.

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Brocke-Heidrich, K., Kretzschmar, A. K., Pfeifer, G., Henze, C., Loffler, D., Koczan, D., Thiesen, H.-J., Burger, R., Gramatzki, M., Horn, F. (2004). Interleukin-6-dependent gene expression profiles in multiple myeloma INA-6 cells reveal a Bcl-2 family-independent survival pathway closely associated with Stat3 activation. Blood 103: 242-251 [Abstract] [Full Text]
Wang, X., Li, Z., Naganuma, A., Ye, B. H. (2002). Negative autoregulation of BCL-6 is bypassed by genetic alterations in diffuse large B cell lymphomas. Proc. Natl. Acad. Sci. USA 99: 15018-15023 [Abstract] [Full Text]
Vasanwala, F. H., Kusam, S., Toney, L. M., Dent, A. L. (2002). Repression of AP-1 Function: A Mechanism for the Regulation of Blimp-1 Expression and B Lymphocyte Differentiation by the B Cell Lymphoma-6 Protooncogene. J. Immunol. 169: 1922-1929 [Abstract] [Full Text]
Lin, K.-I, Angelin-Duclos, C., Kuo, T. C., Calame, K. (2002). Blimp-1-Dependent Repression of Pax-5 Is Required for Differentiation of B Cells to Immunoglobulin M-Secreting Plasma Cells. Mol. Cell. Biol. 22: 4771-4780 [Abstract] [Full Text]
Falini, B., Mason, D. Y. (2002). Proteins encoded by genes involved in chromosomal alterations in lymphoma and leukemia: clinical value of their detection by immunocytochemistry. Blood 99: 409-426 [Abstract] [Full Text]
Fearon, D. T., Manders, P., Wagner, S. D. (2001). Arrested Differentiation, the Self-Renewing Memory Lymphocyte, and Vaccination. Science 293: 248-250 [Abstract] [Full Text]
Baron, B. W., Anastasi, J., Thirman, M. J., Furukawa, Y., Fears, S., Kim, D. C., Simone, F., Birkenbach, M., Montag, A., Sadhu, A., Zeleznik-Le, N., McKeithan, T. W. (2002). The human programmed cell death-2 (PDCD2) gene is a target of BCL6 repression: Implications for a role of BCL6 in the down-regulation of apoptosis. Proc. Natl. Acad. Sci. USA 99: 2860-2865 [Abstract] [Full Text]