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Related Experiment Videos

Receptor editing occurs frequently during normal B cell development

M W Retter1, D Nemazee

  • 1National Jewish Medical and Research Center, Division of Basic Sciences, Department of Pediatrics, Denver, Colorado 80206, USA.

The Journal of Experimental Medicine
|October 9, 1998
PubMed
Summary
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Receptor editing in normal B cells, a process where immunoglobulin genes rearrange, occurs frequently. This mechanism, involving kappa and lambda light chain gene rearrangement, helps prevent self-reactivity in the immune system.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Allelic exclusion normally prevents further immunoglobulin gene rearrangement after initial B cell receptor assembly.
  • However, B cells can undergo receptor editing to alter receptor specificity, particularly in response to self-antigens.
  • This process involves transiently preventing or reversing allelic exclusion through light chain gene rearrangement.

Purpose of the Study:

  • To investigate the frequency of receptor editing in a normal, non-transgenic immune system.
  • To determine if functionally rearranged kappa light chain genes fail to suppress subsequent lambda light chain gene rearrangement.
  • To assess the role of recombining sequence (RS) rearrangements in receptor editing.

Main Methods:

  • Analysis of kappa loci in IgMlambda+ B cells from normal mice.

Related Experiment Videos

  • Identification and analysis of recombined VkappaJkappa genes inactivated by RS rearrangement.
  • Assessment of the frame status of RS-inactivated VkappaJkappa joins.
  • Main Results:

    • Recombining sequence (RS) rearrangements frequently inactivate functionally rearranged kappa loci.
    • Nearly half (47%) of RS-inactivated VkappaJkappa joins were in-frame, indicating successful initial rearrangement.
    • This suggests that kappa gene rearrangement does not always effectively suppress subsequent lambda gene rearrangement.

    Conclusions:

    • Receptor editing occurs at a significantly higher frequency in normal B cells than previously thought.
    • RS recombination appears to be a key mechanism involved in B cell receptor editing.
    • These findings highlight the dynamic nature of B cell receptor repertoire selection in the absence of transgenic manipulation.