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Structure and expression of the human immunoglobulin lambda genes.

T J Vasicek1, P Leder

  • 1Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115.

The Journal of Experimental Medicine
|August 1, 1990
PubMed
Summary
This summary is machine-generated.

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Researchers sequenced human chromosome 22, uncovering a seventh constant lambda (C lambda) gene and detailing the organization of human C lambda complex. This provides insight into immunoglobulin lambda gene evolution and regulation.

Area of Science:

  • Genomics
  • Immunogenetics
  • Molecular Biology

Background:

  • The human immunoglobulin lambda (Ig lambda) light chain locus is complex, with its constant region (C lambda) genes playing a crucial role in antibody function.
  • Understanding the precise organization and evolution of the C lambda complex is essential for comprehending Ig lambda gene expression and potential genetic variations.

Purpose of the Study:

  • To determine the DNA sequence of large regions of human chromosome 22 encompassing the C lambda complex and the 5' region of a rearranged lambda gene.
  • To elucidate the complete structure, organization, and evolutionary history of the human C lambda gene complex.
  • To identify regulatory elements and potential functional elements within the sequenced regions.

Main Methods:

  • DNA sequencing of 33.7 kb containing the C lambda complex and 5.2 kb upstream of the rearranged lambda gene from the U266 myeloma cell line.

Related Experiment Videos

  • Sequence analysis to identify gene structures, pseudogenes, and regulatory motifs.
  • Primer extension analysis to map transcription start sites.
  • In silico analysis for enhancer-like sequences.

    • Main Results:

    • The complete structure of the human C lambda complex was determined, revealing seven C lambda regions organized in a tandem array, each preceded by a J lambda region.
    • A previously undescribed seventh C lambda region was identified, potentially encoding the Ke+Oz- lambda protein. Active genes include lambda 1, 2, 3, and 7; pseudogenes include lambda 4, 5, and 6.
    • The analysis revealed a V lambda pseudogene (psi V lambda 1) and identified the transcription initiation site and promoter elements (TATA box, octamer sequence) of the human lambda gene.
    • No kappa or IgH-like transcriptional enhancers were found in the surrounding 40 kb DNA sequence.

    Conclusions:

    • The human C lambda complex evolved through gene duplication events, likely via unequal crossing over or gene conversion.
    • The amplification of the C lambda complex may be a recent event, possibly originating from an Alu-free DNA segment.
    • The identified promoter elements and the absence of known enhancer sequences suggest a complex, developmentally regulated mechanism for transcriptional activation of human lambda genes.