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Transcription factor NF-kappa B regulates Ig lambda light chain gene rearrangement
H H Bendall1, M L Sikes, E M Oltz
1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|June 22, 2001
Summary
Nuclear factor-kappa B (NF-kappaB) regulates immunoglobulin lambda (Iglambda) gene accessibility and recombination in developing B cells. This transcription factor is crucial for Iglambda accessibility, independent of known promoter elements.
Area of Science:
- Immunology
- Molecular Biology
- Cellular Biology
Background:
- V(D)J recombinase mediates immunoglobulin (Ig) and T-cell receptor (TCR) gene assembly in lymphocytes.
- Gene accessibility, regulated by transcription factors and enhancer elements, directs recombinase activity.
- NF-kappaB regulates Igkappa locus rearrangement, but Iglambda locus control elements lack NF-kappaB binding sites.
Purpose of the Study:
- To investigate the role of NF-kappaB in Iglambda gene regulation in precursor B cells.
- To determine if NF-kappaB influences Iglambda accessibility and recombination.
Main Methods:
- Repression of NF-kappaB activity in precursor B cells.
- Analysis of germline transcription and recombination of Iglambda gene segments.
- Molecular assessment of recombinase accessibility and promoter/enhancer element activity.
Main Results:
- NF-kappaB repression inhibited Iglambda germline transcription and recombination.
- The inhibition occurred at the level of recombinase accessibility, not promoter/enhancer activity.
- Known Iglambda promoter and enhancer activities remained unaffected by NF-kappaB impairment.
Conclusions:
- NF-kappaB controls recombinational accessibility at both immunoglobulin light chain loci (Igkappa and Iglambda).
- Findings suggest a novel NF-kappaB-activated regulatory element for Iglambda during early B cell development.
- This expands the known functions of NF-kappaB in precursor B cells beyond Igkappa regulation.
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