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Generation and function of natural self-reactive B lymphocytes
1Department of Microbiology, University of Alabama at Birmingham 35294-3300, USA.
Seminars in Immunology
|February 1, 1996
Summary
Natural self-reactive B cells are generated through positive selection but may be blocked from maturing. This prevents the production of pathogenic autoreactive antibodies, highlighting immune tolerance mechanisms.
Area of Science:
- Immunology
- Molecular Biology
Background:
- Understanding B cell development and self-tolerance is crucial for autoimmune disease research.
- Developmentally restricted VH gene expression plays a role in B cell repertoire formation.
Purpose of the Study:
- To investigate the role of VH81X-mu-heavy chain expression in B cell development and self-reactivity.
- To analyze the impact of self-antigen selection on B cell maturation and antibody production.
Main Methods:
- Construction and analysis of VH81X-mu-heavy chain transgenic mice.
- Flow cytometry to analyze B cell subsets (CD23-/IgMhi and CD23+ IgMlo).
- Administration of antibodies to assess the impact on B cell generation.
Main Results:
- Transgenic B cells predominantly expressed the VH81X-mu-heavy chain with kappa light chains and were self-reactive.
- A population of self-reactive B cells with identical antigen receptors was identified at the CD23-/IgMhi stage.
- Post-natal antibody administration significantly reduced the generation of these self-reactive B cells.
Conclusions:
- Self-reactive B cells are continuously generated via positive selection but can be arrested at the CD23-/IgMhi stage.
- Maturation arrest prevents T cell help and the production of pathogenic autoreactive IgG antibodies.
- This mechanism contributes to maintaining self-tolerance and preventing autoimmunity.