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Tolerance induction in resting memory B cells specific for a protein antigen
1Department of Microbiology, University of Minnesota Medical School, Minneapolis 55455.
Journal of Immunology (Baltimore, Md. : 1950)
|May 1, 1992
Summary
Resting memory B lymphocytes can be induced into a tolerant state by specific antigen exposure. This B cell tolerance is antigen-specific and involves cellular signaling pathways.
Area of Science:
- Immunology
- Cellular Biology
- B lymphocyte research
Background:
- Resting memory B lymphocytes are crucial for adaptive immunity.
- Tolerance induction is a key mechanism for preventing autoimmunity.
- Previous studies showed immature B cells are susceptible to tolerance.
Purpose of the Study:
- To investigate tolerance induction in resting memory B lymphocytes.
- To determine factors influencing B cell tolerance.
- To elucidate the signaling pathways involved in B cell nonresponsiveness.
Main Methods:
- In vitro splenic fragment cultures.
- Incubation of memory B cells with model antigen (cytochrome c polymer).
- Assessment of B cell responsiveness and signaling pathway involvement (protein tyrosine kinase inhibitors, T cell activation).
Main Results:
- Greater than 80% of Ag-specific memory B cells became unresponsive after 24h incubation with 1 microM cytochrome polymer.
- Induced nonresponsiveness was antigen-specific and not due to surface Ig receptor blockade.
- T cell help was not required, but direct T cell activation partially inhibited tolerance; protein tyrosine kinase inhibitors partially blocked tolerance induction.
Conclusions:
- Resting memory B cells can be rendered tolerant in vitro.
- Tolerance induction depends on antigen interaction strength and involves cellular signaling.
- Tyrosine phosphorylation plays a role in establishing B cell nonresponsiveness.