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

Correspondence to: Douglas T. Fearon, Wellcome Trust Immunology Unit, MRC Centre, Hills Road, Cambridge CB2 2SP, UK. Tel:44-1223-330528 Fax:44-1223-336817 E-mail: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

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