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Tolerance susceptibility of newly generating memory B cells
P J Linton1, A Rudie, N R Klinman
1Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, CA 92037.
Journal of Immunology (Baltimore, Md. : 1950)
|June 15, 1991
Summary
Newly generated memory B cells can become susceptible to self-antigen recognition and inactivation. This B cell tolerance window emerges after initial antigen exposure, impacting immune responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- Newly forming memory B cells acquire somatic mutations, potentially leading to self-recognition.
- The emergence of secondary B cells may involve a period of heightened susceptibility to tolerance induction.
Purpose of the Study:
- To investigate if newly generated memory B cells are susceptible to tolerance induction.
- To determine the characteristics and timing of this potential tolerance susceptibility window.
Main Methods:
- In vitro generation of memory B cells with and without tolerogen.
- Assessment of B cell inactivation following antigenic stimulation.
- Analysis of tolerance induction in the presence of free hapten, competing immunogen, and cross-reactive determinants.
Main Results:
- Precursors to memory B cells are resistant to tolerance before antigenic stimulation.
- Newly emerging secondary B cells (2-7 days post-stimulation) are susceptible to inactivation by tolerogen.
- Inactivation is less specific than in immature B cells and can be blocked by free hapten or competed by immunogen.
- Tolerance induction after primary stimulation does not prevent subsequent responses to a third stimulation.
Conclusions:
- Newly emerging memory B cells exhibit a transient window of susceptibility to inactivation.
- The clonal progression to memory B cells appears resistant to tolerance induction, despite transient susceptibility of individual cells.