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Molecular basis for the interaction between human IgM and staphylococcal protein A
M Hakoda1, S Hayashimoto, H Yamanaka
1Institute of Rheumatology, Tokyo Women's Medical College, Japan.
Clinical Immunology and Immunopathology
|September 1, 1994
Summary
Staphylococcal protein A (SPA) acts as a superantigen in humans, selectively activating B cells expressing specific VH3 genes. This leads to the production of IgM antibodies with varying reactivity to SPA.
Area of Science:
- Immunology
- Molecular Biology
- B cell biology
Background:
- Immunoglobulin (IgM) gene usage and antigen reactivity are crucial for immune responses.
- Staphylococcal protein A (SPA) is a known bacterial protein with potential immunomodulatory effects.
Purpose of the Study:
- To investigate the association between VH gene usage and immunoglobulin reactivity.
- To determine if SPA influences B cell activation and antibody production.
Main Methods:
- Cloning of B cells from adult and neonatal human blood via EBV transformation.
- Characterization of B cell clones producing IgM reactive with SPA.
- Analysis of VH gene usage, light chain usage, and antibody binding avidity.
- Sequencing of VH3-IgM clones to analyze gene configuration and complementarity determining regions.
Main Results:
- Approximately one-third of B cell clones produced IgM reactive with SPA.
- All SPA-reactive IgM clones utilized VH3 genes, while non-reactive clones did not.
- SPA-reactive IgM antibodies exhibited differential binding avidity to SPA.
- VH3 genes in SPA-reactive IgM were used in a near-germline configuration.
Conclusions:
- SPA functions as a superantigen in humans, driving the selection of B cells expressing specific VH3 genes.
- Restricted VH3 gene usage and near-germline configuration suggest a targeted B cell activation mechanism by SPA.