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Related Experiment Videos

Soluble antigen profoundly reduces memory B-cell numbers even when given after challenge immunization

G J Nossal1, M Karvelas, B Pulendran

  • 1Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.

Proceedings of the National Academy of Sciences of the United States of America
|April 1, 1993
PubMed
Summary

This study reveals that T-cell help is crucial for generating memory B cells. Soluble toleragen can silence activated T cells, preventing memory B cell formation and demonstrating a novel approach to immune tolerance.

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Area of Science:

  • Immunology
  • B-cell biology
  • T-cell immunology

Background:

  • Examining the splenic B-cell repertoire for high-affinity anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) B cells requires specific methods.
  • Naive spleens contain few high-affinity anti-NP B cells, but immunization rapidly increases their numbers.

Purpose of the Study:

  • To investigate the role of T-cell help in memory B-cell generation.
  • To explore the efficacy of soluble toleragen in preventing the development of anti-NP antibody-forming cell precursors.

Main Methods:

  • Utilized a dual strategy involving polyclonal B-cell activation and a high-affinity specific enzyme-linked immunosorbent assay (ELISA).
  • Administered soluble NP2-human serum albumin (HSA) as a toleragen to assess its impact on B-cell precursor development.

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  • Investigated the role of T and B cells by comparing NP2-HSA with HSA and NP-conjugated irrelevant carriers.

    • Main Results:

    • Thymus-dependent immunization led to the appearance of approximately 10(5) high-affinity anti-NP B cells per spleen within two weeks.
    • A single injection of NP2-HSA toleragen significantly reduced the development of these B-cell precursors, even when administered days after immunization.
    • Soluble HSA showed partial tolerance, while NP conjugated to irrelevant carriers was less effective, suggesting a role for T and B cells.

    Conclusions:

    • Continuing T-cell help is essential for the generation of memory B cells.
    • Recently activated T cells involved in memory B-cell generation can be effectively silenced in vivo using soluble toleragen.
    • These findings highlight a potential strategy for inducing immune tolerance by targeting T-cell help during B-cell activation.