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BCL6 is critical for the development of a diverse primary B cell repertoire
- Source :
- The Journal of experimental medicine, vol 207, iss 6, The Journal of Experimental Medicine
- Publication Year :
- 2010
- Publisher :
- Rockefeller University Press, 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-7Rα–Stat5 signaling negatively regulates BCL6. Upon productive VH-DJH gene rearrangement and expression of a μ heavy chain, however, activation of pre–B cell receptor signaling strongly induces BCL6 expression, whereas IL-7Rα–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 :
- Transcription, Genetic
Apoptosis
Medical and Health Sciences
Mice
0302 clinical medicine
hemic and lymphatic diseases
Gene Rearrangement, B-Lymphocyte, Light Chain
Immunology and Allergy
Cells, Cultured
Recombination, Genetic
Gene Rearrangement
B-Lymphocytes
0303 health sciences
Cultured
ADP-Ribosylation Factors
Lymphopoiesis
B-Lymphocyte
BCL6
Up-Regulation
DNA-Binding Proteins
medicine.anatomical_structure
Pre-B Cell Receptors
Proto-Oncogene Proteins c-bcl-6
Signal transduction
Transcription
Signal Transduction
Light Chain
Cell Survival
Precursor Cells
Cells
Molecular Sequence Data
Immunology
Down-Regulation
Somatic hypermutation
Biology
Article
Proto-Oncogene Proteins c-myc
03 medical and health sciences
Genetic
medicine
Animals
Humans
B cell
Cell Proliferation
B-Lymphoid
030304 developmental biology
Base Sequence
Cell growth
Precursor Cells, B-Lymphoid
Interleukin-7
Germinal center
Gene rearrangement
Molecular biology
Recombination
Cytoprotection
DNA Damage
030215 immunology
Subjects
Details
- ISSN :
- 15409538 and 00221007
- Volume :
- 207
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....44bb09e61ea279fb12d20ec71aa83d9b