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IRF-4,8 orchestrate the pre-B-to-B transition in lymphocyte development
Runqing Lu1, Kay L Medina, David W Lancki
1Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
Genes & Development
|July 2, 2003
Summary
Interferon regulatory factors IRF-4 and IRF-8 are crucial for B-cell development, regulating immunoglobulin light-chain gene rearrangement and the transition from pre-B to B cells.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- B-lymphocyte development requires sequential DNA rearrangements of immunoglobulin (Ig) genes.
- This process depends on the transient expression of pre-antigen receptor complexes (pre-BCR).
- Transcription factors coordinating the pre-B to B cell transition remain unidentified.
Purpose of the Study:
- To identify transcription factors essential for the pre-B to B cell transition.
- To investigate the role of interferon regulatory factors (IRFs) in B-cell development.
Main Methods:
- Genetic analysis of B-cell development.
- Molecular analysis of immunoglobulin gene rearrangement.
- Study of IRF-4 (Pip) and IRF-8 (ICSBP) function in B-cell development.
Main Results:
- IRF-4 and IRF-8 are required for immunoglobulin light-chain gene rearrangement, but not heavy-chain.
- Absence of IRF-4 and IRF-8 arrests B-cell development at the cycling pre-B-cell stage.
- Mutant cells lacking IRF-4 and IRF-8 fail to down-regulate the pre-BCR.
Conclusions:
- IRF-4 and IRF-8 act as a genetic switch in B-cell development.
- These factors down-regulate surrogate light-chain gene expression.
- IRF-4 and IRF-8 induce conventional light-chain gene transcription and rearrangement.