Suppression of signal transducer and activator of transcription 3-dependent B lymphocyte terminal differentiation by BCL-6.
Lymphocytes usually differentiate into effector cells within days after antigen exposure, except in germinal centers where terminal differentiation is delayed while somatic hypermutation creates high-affinity antibody mutants. Here we investigate whether arrest of terminal differentiation can be mediated by BCL-6, a transcriptional repressor that is expressed by germinal center B cells and is required for this phase of B cell development. We find that BCL-6 suppresses the differentiation of transformed and primary B cells to plasma cells by inhibiting the signal transducer and activator of transcription 3-dependent expression 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 differentiation may also underlie the association between chromosomal translocations of its gene and B cell lymphomas.
Reljic
R
R
Wellcome Trust Immunology Unit, University of Cambridge, School of Clinical Medicine, Cambridge CB2 2SP, United Kingdom.
Wagner
S D
SD
Peakman
L J
LJ
Fearon
D T
DT
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D051379:Mice; D010950:Plasma Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D016207:Cytokines; D004268:DNA-Binding Proteins; C513258:Prdm1 protein, mouse; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1