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Special Features of Adaptive Immunity01:20

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Updated: Oct 7, 2025

In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients
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Adaptive tolerance: Protection through self-recognition.

Timm Amendt1, Hassan Jumaa1

  • 1Institute of Immunology, University Hospital Ulm, Ulm, Germany.

Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology
|January 5, 2022
PubMed
Summary
This summary is machine-generated.

Autoreactive B cells can be activated by self-antigen complexes, leading to adaptive tolerance. This novel mechanism involves high-affinity IgM autoantibodies protecting self-targets from degradation.

Keywords:
B cellsIgDIgMautoantibodiesautoimmunitytolerance

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Area of Science:

  • Immunology
  • Autoimmunity
  • B cell biology

Background:

  • Immunoglobulin gene rearrangement generates self-reactive B cells, necessitating tolerance mechanisms for homeostasis.
  • Existing central and peripheral tolerance models do not fully account for the prevalence of autoimmune diseases.
  • Recent studies indicate autoreactive B cells can respond, not just be deleted or anergized, in physiological conditions.

Purpose of the Study:

  • To propose a novel mechanism for the activation of autoreactive B cells under physiological conditions.
  • To introduce the concept of 'adaptive tolerance' mediated by autoantibody production.
  • To explore the role of high-affinity IgM autoantibodies in this process.

Main Methods:

  • The study proposes a theoretical framework based on recent physiological mouse model findings.
  • It discusses the proposed mechanism of autoreactive B cell activation by polyvalent autoantigen complexes.
  • Analysis of the role of repeated autoantigen complex encounters in affinity maturation of IgM autoantibodies.

Main Results:

  • Autoreactive B cells are activated by polyvalent autoantigen complexes, challenging current tolerance paradigms.
  • This activation leads to the production of affinity-matured autoreactive IgM.
  • The generated IgM autoantibodies protect self-targets from degradation, a key feature of adaptive tolerance.

Conclusions:

  • A novel mechanism termed 'adaptive tolerance' is proposed, involving autoreactive B cell activation and IgM autoantibody production.
  • High-affinity IgM autoantibodies play an unexpected role in protecting self-tissues.
  • This discovery offers a new perspective on the regulation of autoimmunity and B cell tolerance.