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Low molecular weight antigen arrays delete high affinity memory B cells without affecting specific T-cell help
J W Reim1, D E Symer, D C Watson
1Department of Biophysics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Molecular Immunology
|December 1, 1996
Summary
Low molecular weight polymers with multiple epitopes suppress antibody responses by eliminating high-affinity B cells. This functional deletion of antigen-specific B cells, even with T-cell help, suggests physical deletion and long-term immune suppression.
Area of Science:
- Immunology
- Cellular immunology
Background:
- T-cell dependent antibody responses can be suppressed by specific antigen arrays.
- High-affinity memory B cells are crucial for secondary antibody responses.
Purpose of the Study:
- To investigate the mechanism by which antigen arrays suppress T-cell dependent antibody responses.
- To determine if suppression involves the elimination of epitope-specific B cells.
Main Methods:
- Adoptive transfer of splenocytes from suppressed and unsuppressed donors into irradiated recipients.
- Antigenic challenge and assessment of secondary anti-hapten antibody response.
- Flow cytometry to quantify hapten-specific B cells.
- Assessment of T-cell help by carrier-primed T cells.
Main Results:
- Adoptively transferred splenocytes from suppressed donors failed to reconstitute a secondary antibody response.
- Suppression was dose- and duration-dependent, with minimal antigen array carryover.
- T-cell help for B cells remained intact, but B cell responsiveness was lost.
- Flow cytometry revealed a marked reduction in hapten-specific B cells following suppression.
Conclusions:
- Suppressive antigen arrays induce long-term functional elimination of high-affinity, antigen-specific B cells.
- This elimination occurs despite adequate T-cell help, indicating a B cell-intrinsic defect.
- The long-term suppression suggests physical deletion of the antigen-specific B cell population.