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Related Experiment Videos

B cell positive selection by soluble self-antigen.

Sylvie Julien1, Pauline Soulas, Jean-Claude Garaud

  • 1Laboratoire d'Immunopathologie, Institut d'Hématologie et d'Immunologie, 1 place de l'hôpital, 67091 Strasbourg Cedex, France.

Journal of Immunology (Baltimore, Md. : 1950)
|October 9, 2002
PubMed
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Natural autoreactive B cells are positively selected by self-antigens, challenging traditional negative selection models. This selection depends on IgD and occurs in the spleen, favoring marginal zone B cells.

Area of Science:

  • Immunology
  • Autoimmunity
  • B cell biology

Background:

  • Autoreactive B cells typically undergo negative selection to prevent autoimmunity.
  • Natural autoreactive B cells (nAAbs) producing low-affinity autoantibodies are paradoxically frequent.
  • Previous work established transgenic mouse models for human nAAb production.

Purpose of the Study:

  • To investigate the selection mechanisms of natural autoreactive B cells.
  • To determine the role of self-antigen binding in B cell selection.
  • To elucidate the influence of IgD and IgG on autoreactive B cell populations.

Main Methods:

  • Generation of transgenic mouse lines expressing human nAAb (binding ssDNA and Fcgamma).
  • Crossing nAAb-transgenic mice with mice expressing knockin chimeric IgG.

Related Experiment Videos

  • Analysis of B cell development, subset distribution, and selection in spleen.

    • Main Results:

    • Constitutive expression of chimeric IgG increased nAAb-expressing B cells.
    • This positive selection was dependent on the presence of IgD.
    • Selection occurred in the spleen, affecting all mature B cell subsets, with enrichment in marginal zone B cells.

    Conclusions:

    • Soluble self-antigens can mediate positive clonal selection of autoreactive B cells.
    • IgD plays a critical role in the positive selection of natural autoreactive B cells.
    • These findings challenge the paradigm of strict negative selection for all autoreactive B cells.