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Development and function of the early B cell repertoire.
J F Kearney1, J Bartels, A M Hamilton
1Department of Microbiology, University of Alabama, Birmingham 35294.
International Reviews of Immunology
|January 1, 1992
Summary
The early B cell repertoire exhibits inherent autoreactivity and multispecificity due to limited genetic diversity and germline gene usage. These characteristics are crucial for establishing self-tolerance and shaping the adult immune system during development.
Area of Science:
- Immunology
- Molecular Biology
- Developmental Biology
Background:
- The early B cell repertoire is known for its interconnectedness, autoreactivity, and multispecificity.
- Understanding the molecular basis of these characteristics is key to comprehending B cell development and immune system maturation.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the multispecificity and autoreactivity of early B cells.
- To analyze the role of specific VH gene segments and CDR3 regions in shaping the early B cell repertoire.
Main Methods:
- Sequence analysis of VH gene rearrangements in early B cells.
- Isolation and characterization of hybridomas secreting IgM antibodies from specific VH gene families.
- Analysis of amino acid composition in VH regions of selected antibodies.
Main Results:
- Identified shared or identical CDR3 regions resulting from germline gene segment usage without N region addition.
- Observed frequent usage of D proximal VH genes, characteristic of the early B cell repertoire.
- Isolated functional IgM antibodies using the VH81X gene, exhibiting broad multireactivity potentially due to charged amino acid groups.
Conclusions:
- Genetic restrictions and limited somatic mutation in the early B cell repertoire contribute to its self-reactivity.
- Antibodies utilizing specific VH genes, like VH81X, display unique cross-reactivity patterns, suggesting a distinct role in B cell development.
- The prevalence of specific VHDJH genes and DJH joins in early B cells underlies anti-lymphocyte reactivity and may guide the development of the adult repertoire.