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Related Experiment Videos

Murine lambda gene rearrangements: the stochastic model prevails over the ordered model.

B Nadel1, P A Cazenave, P Sanchez

  • 1Département d'Immunologie, Institut Pasteur (URA CNRS 359 and Université Pierre et Marie Curie), Paris, France.

The EMBO Journal
|February 1, 1990
PubMed
Summary
This summary is machine-generated.

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Mammalian B cell immunoglobulin gene rearrangement, specifically for lambda light chains, appears stochastic rather than ordered. Most B cells undergo a single rearrangement, suggesting lambda immunoglobulin is not essential for exclusion mechanisms.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Mammalian B cell immunoglobulin (Ig) gene rearrangement typically follows an ordered sequence: heavy chain, then kappa light chain, then lambda light chain.
  • The murine lambda locus's genomic organization allows for potential simultaneous expression of multiple subtypes from a single chromosome.

Purpose of the Study:

  • To investigate whether immunoglobulin gene rearrangement in B cells follows an ordered or stochastic model, focusing on the lambda locus.
  • To analyze V lambda J lambda rearrangements in B cell hybridomas to determine the predominant rearrangement model.

Main Methods:

  • Analysis of V lambda J lambda rearrangements in a panel of 67 B cell hybridomas secreting different lambda subtypes (lambda 1, lambda 2, lambda 3, lambda x).
  • Detection of kappa allele rearrangement and RS recombination within the analyzed hybridomas.

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Main Results:

  • A single V lambda J lambda rearrangement was observed in 97% of cases, strongly supporting a stochastic rearrangement model over an ordered one.
  • The potential for a secondary productive rearrangement after an initial aberrant one is rare.
  • Kappa allele rearrangement occurred in 97% of cases, and RS recombination was detected in 77%, suggesting a role in lambda locus activation.

Conclusions:

  • The lambda immunoglobulin gene rearrangement process in B cells is predominantly stochastic, not ordered.
  • Lambda immunoglobulin may not be strictly required for ensuring allelic and subtypic exclusion mechanisms.
  • RS recombination acts as a trans-acting, though dispensable, activator for the lambda locus, even though kappa locus stimulation precedes lambda.