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Published on: April 11, 2019
B-cell tolerance checkpoints in health and autoimmunity
1Hospital for Special Surgery, Weill Medical College of Cornell University, New York, NY 10021, USA. meffree@hss.edu
Current Opinion in Immunology
|October 14, 2008
Summary
Antibody diversity arises from V(D)J recombination and somatic hypermutation, crucial for immunity but also potentially causing autoimmunity. Defects in B cell tolerance checkpoints can lead to autoimmune diseases.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Antibody repertoire diversity is essential for adaptive immunity.
- Two primary mechanisms generate antibody diversity: V(D)J recombination and somatic hypermutation (SHM).
- These processes can inadvertently create autoantibodies, potentially leading to autoimmunity.
Purpose of the Study:
- To explain the mechanisms generating antibody diversity.
- To highlight the dual role of antibody diversity in immunity and autoimmunity.
- To discuss the link between B cell tolerance defects and autoimmune diseases.
Main Methods:
- Review of established immunological and genetic mechanisms.
- Analysis of B cell development and tolerance pathways.
- Correlation of tolerance defects with human autoimmune conditions.
Main Results:
- V(D)J recombination generates diversity in early B-cell development.
- Somatic hypermutation further diversifies antibody genes in mature B cells.
- Dysregulation of B cell tolerance checkpoints contributes to autoimmunity.
Conclusions:
- Antibody gene recombination and SHM are vital for humoral immunity.
- Failures in central and peripheral B cell tolerance can result in autoantibody production.
- Defects in these tolerance mechanisms are implicated in human autoimmune disorders.
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