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Related Experiment Videos

Chronic graft-versus-host reaction is associated with a decrease in Ig light chain receptor editing in bone marrow

Nili Feuerstein1, Dennis C DeSimone, Robert A Eisenberg

  • 1Division of Rheumatology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, 19104, USA. feuerstein@email.chop.edu

European Journal of Immunology
|April 29, 2004
PubMed
Summary

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Chronic graft-versus-host reaction (GVH) prevents B cell anergy by reducing receptor editing in immature self-reactive B cells. This decrease in receptor editing allows B cells to escape tolerance, potentially leading to autoimmunity.

Area of Science:

  • Immunology
  • Autoimmunity
  • B cell development

Background:

  • Self-antigen encounter during B cell development typically induces anergy or receptor editing.
  • Chronic graft-versus-host reaction (GVH) has been shown to prevent B cell anergy in tolerant mice.

Purpose of the Study:

  • To investigate the effect of chronic GVH on receptor editing in immature self-reactive B cells.
  • To elucidate the mechanisms by which chronic GVH impacts B cell tolerance.

Main Methods:

  • Analysis of B cell populations in tolerant Ig/sHEL mice undergoing chronic GVH.
  • Quantification of endogenous kappa light chain rearrangements.
  • Measurement of recombinase-activating gene (RAG)-2 expression in immature B cells.

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Main Results:

  • Chronic GVH markedly reduced the population of 'receptor-edited' B cells.
  • Self-reactive B cells in GVH mice exhibited reduced endogenous kappa chain rearrangements.
  • RAG-2 expression was significantly decreased in immature self-reactive B cells from chronic GVH mice.

Conclusions:

  • Chronic GVH impairs receptor editing in immature self-reactive B cells within the bone marrow.
  • Newly emerging B cells may escape tolerance in chronic GVH due to decreased receptor editing.
  • Autoimmunity in chronic GVH may arise from a failure of B cell tolerance at multiple checkpoints.