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Interrogating Individual Autoreactive Germinal Centers by Photoactivation in a Mixed Chimeric Model of Autoimmunity
Published on: April 11, 2019
B cell receptor editing in tolerance and autoimmunity.
Eline T Luning Prak1, Marc Monestier, Robert A Eisenberg
1Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. luning@mail.med.upenn.edu
Annals of the New York Academy of Sciences
|January 22, 2011
Summary
Receptor editing allows lymphocytes with self-reactive antigen receptors to alter their specificity through gene rearrangement, complicating established theories of immune cell development and antibody repertoire formation.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Lymphocytes normally cease antibody gene rearrangement after expressing a functional antigen receptor, a process known as allelic exclusion.
- Autoreactive lymphocytes can evade negative selection by undergoing receptor editing, modifying their antigen receptor specificity.
- This editing process challenges the Clonal Selection Hypothesis by allowing for receptor plasticity.
Purpose of the Study:
- To describe the discovery and mechanisms of receptor editing in lymphocytes.
- To elucidate the pathways of receptor editing at the heavy (H) and light (L) chain loci.
- To review current evidence on the occurrence and impact of receptor editing on the antibody repertoire.
Main Methods:
- Discovery and characterization of receptor editing.
- Analysis of heavy and light chain gene rearrangement pathways.
- Review of existing evidence on the mechanisms and consequences of receptor editing.
Main Results:
- Receptor editing provides a mechanism for lymphocytes with autoreactive receptors to escape negative selection.
- Editing involves additional antibody gene rearrangements, potentially altering receptor specificity.
- Incomplete inactivation of initial immunoglobulin genes during editing can lead to B cells expressing two specificities, violating allelic exclusion.
Conclusions:
- Receptor editing is a critical process that allows for the modification of antigen receptor specificities in developing lymphocytes.
- It complicates the understanding of immune cell development and the stability of the antibody repertoire.
- Further research is needed to fully understand the intricate mechanisms and broad effects of receptor editing.
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