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

• DOI: 10.1084/jem.192.12.1841
• Publication Date: 2002-07-26T16:48:33Z
• Authors: Rajko Reljic; Simon D. Wagner; Luke J. Peakman; Douglas T. Fearon
• Keywords: STAT3 Transcription Factor; 0301 basic medicine; 570; B-Lymphocytes; Cell Survival; Plasma Cells; Cell Differentiation; Flow Cytometry; Cell Line; DNA-Binding Proteins; Repressor Proteins; Mice; 03 medical and health sciences; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-6; Trans-Activators; Animals; Cytokines; Positive Regulatory Domain I-Binding Factor 1; Cell Division; Transcription Factors

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.