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Wild mice express an Ig V lambda gene that differs from any V lambda in BALB/c but resembles a human V lambda

L S Reidl1, C M Kinoshita, L A Steiner

  • 1Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.

Journal of Immunology (Baltimore, Md. : 1950)
|July 15, 1992
PubMed
Summary

Wild mice possess diverse lambda light chain variable (V lambda) genes, some resembling human sequences and potentially linked to amyloidosis, unlike laboratory strains. This suggests broader mammalian V lambda gene diversity than previously understood.

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Area of Science:

  • Immunogenetics
  • Molecular Biology
  • Mammalian Genetics

Background:

  • Laboratory inbred mouse strains, like BALB/c, have a limited number of germ-line lambda light chain genes (V lambda and J lambda-C lambda).
  • Previous studies suggested wild mice might possess a more extensive repertoire of C lambda genes based on DNA hybridization.

Purpose of the Study:

  • To investigate the diversity and expression of lambda light chain genes in wild mice.
  • To determine the sequence of cDNA encoding lambda chains in hybridomas from wild Mus musculus subspecies.

Main Methods:

  • Sequencing of cDNA encoding lambda light chains from hybridomas derived from wild mice.
  • Sequence comparison of V lambda, J lambda, and C lambda regions with known murine and human sequences.
  • Southern blotting to analyze the presence of specific V lambda genes in BALB/c mice.

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Main Results:

  • Two hybridomas produced lambda L chains with V lambda regions showing only ~40% amino acid identity to known murine V lambda but closer similarity to human V lambda, particularly subgroup VI.
  • These human-like V lambda sequences share an unusual insertion in framework 3, a feature associated with amyloid deposits.
  • A third hybridoma's L chain V lambda resembled BALB/c V lambda 1, while all three shared identical J lambda and C lambda segments, indicating preferential expression of one gene.

Conclusions:

  • Wild mice harbor a greater diversity of lambda light chain V lambda genes than inbred strains, including sequences similar to human V lambda.
  • The presence of human-like V lambda genes in wild mice suggests their potential widespread occurrence in mammalian populations.
  • Despite potential gene expansion in wild mice, a single J lambda-C lambda gene appears to be preferentially expressed.