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Related Experiment Videos

Deconstructing B cell tolerance to basement membranes.

Mary H Foster1, Ying Zhang, Amy G Clark

  • 1Department of Medicine, Duke University, Durham Veterans Affairs Medical Centers, Durham, NC 27710, USA. mhfoster@duke.edu

Archivum Immunologiae Et Therapiae Experimentalis
|July 11, 2006
PubMed
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Autoantibodies targeting basement membrane antigens are common in autoimmunity. Studies show that autoreactive B cells against laminin are actively regulated, preventing autoimmune disease even in susceptible mice.

Area of Science:

  • Immunology
  • Autoimmunity Research
  • Molecular Biology

Background:

  • Basement membrane antigens are common targets in systemic and organ-restricted autoimmunity.
  • These matrices have limited epitope exposure, complicating the study of autoimmune responses.
  • Understanding humoral autoimmunity to basement membrane antigens is crucial for developing treatments.

Purpose of the Study:

  • To dissect mechanisms controlling humoral autoimmunity to nephritogenic basement membrane antigens.
  • To develop and utilize autoantibody transgenic mouse models to study tolerance induction.
  • To assess the regulation of autoreactivity to laminin and collagen, and to cryptic epitopes.

Main Methods:

  • Development of autoantibody transgenic mouse models, including one for laminin (LamH Ig transgene).

Related Experiment Videos

  • Analysis of B cell regulation mechanisms such as central deletion, kappa light-chain editing, and anergy.
  • Assessment of tolerance in autoimmune-prone genetic backgrounds (MRL, BXSB) and under environmental stimulation.
  • Introduction of a novel anti-collagen transgenic model to study distinct basement membrane epitopes.

    • Main Results:

    • Autoreactive B cells specific for laminin are generated but actively regulated in vivo.
    • Mechanisms of immunological censorship, including deletion and anergy, maintain tolerance.
    • Tolerance to anti-laminin B cells is maintained in autoimmune-susceptible genetic backgrounds and despite environmental provocation.
    • Pathogenic anti-laminin reactivity in systemic lupus is shown to be tightly regulated.

    Conclusions:

    • Humoral autoimmunity to basement membrane antigens is tightly regulated by multiple tolerance mechanisms.
    • Transgenic models provide valuable insights into the control of autoreactive B cells.
    • Further studies with anti-collagen models will elucidate regulation of organ-restricted autoimmune responses.
    • These findings pave the way for novel strategies to treat autoimmune diseases by targeting autoreactive cells.