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BCL6 is critical for the development of a diverse primary B cell repertoire.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2010 Jun 07; Vol. 207 (6), pp. 1209-21. Date of Electronic Publication: 2010 May 24. - Publication Year :
- 2010
-
Abstract
- BCL6 protects germinal center (GC) B cells against DNA damage-induced apoptosis during somatic hypermutation and class-switch recombination. Although expression of BCL6 was not found in early IL-7-dependent B cell precursors, we report that IL-7Ralpha-Stat5 signaling negatively regulates BCL6. Upon productive VH-DJH gene rearrangement and expression of a mu heavy chain, however, activation of pre-B cell receptor signaling strongly induces BCL6 expression, whereas IL-7Ralpha-Stat5 signaling is attenuated. At the transition from IL-7-dependent to -independent stages of B cell development, BCL6 is activated, reaches expression levels resembling those in GC B cells, and protects pre-B cells from DNA damage-induced apoptosis during immunoglobulin (Ig) light chain gene recombination. In the absence of BCL6, DNA breaks during Ig light chain gene rearrangement lead to excessive up-regulation of Arf and p53. As a consequence, the pool of new bone marrow immature B cells is markedly reduced in size and clonal diversity. We conclude that negative regulation of Arf by BCL6 is required for pre-B cell self-renewal and the formation of a diverse polyclonal B cell repertoire.
- Subjects :
- ADP-Ribosylation Factors metabolism
Animals
Apoptosis
Base Sequence
Cell Proliferation
Cell Survival
Cells, Cultured
Cytoprotection
DNA Damage genetics
Down-Regulation genetics
Gene Rearrangement, B-Lymphocyte, Light Chain genetics
Humans
Interleukin-7 metabolism
Lymphopoiesis
Mice
Molecular Sequence Data
Pre-B Cell Receptors metabolism
Precursor Cells, B-Lymphoid cytology
Precursor Cells, B-Lymphoid metabolism
Proto-Oncogene Proteins c-bcl-6
Proto-Oncogene Proteins c-myc metabolism
Recombination, Genetic genetics
Signal Transduction
Transcription, Genetic
Up-Regulation genetics
B-Lymphocytes cytology
B-Lymphocytes immunology
DNA-Binding Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1540-9538
- Volume :
- 207
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 20498019
- Full Text :
- https://doi.org/10.1084/jem.20091299