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Related Experiment Videos

Antibody-independent complement activation by myelin via the classical complement pathway.

J C Cyong, S S Witkin, B Rieger

    The Journal of Experimental Medicine
    |February 1, 1982
    PubMed
    Summary

    Dimerized myelin basic protein (MBP) activates the human complement system independently of antibodies. This discovery sheds light on complement activation in neurological disorders.

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    Area of Science:

    • Neuroimmunology
    • Complement System Biology

    Background:

    • The human complement system can be activated by antibody-independent pathways.
    • Brain tissue components may interact with the complement system.

    Purpose of the Study:

    • To investigate the role of myelin basic protein (MBP) in complement activation.
    • To explore the developmental acquisition of complement-activating properties in murine brain.

    Main Methods:

    • Activation of human complement by murine and rabbit brain homogenates.
    • Fractionation of murine brain to isolate myelin and myelin basic protein (MBP).
    • Chemical cross-linking of MBP to form dimers and assess complement activation.

    Main Results:

    • Murine and rabbit brain homogenates activated human complement via the classical pathway in an antibody-independent manner, requiring calcium ions.

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  • Complement-activating activity was localized to the myelin fraction of murine brain.
  • Dimerized MBP, but not monomeric MBP, demonstrated significant anticomplementary activity.
  • The capacity of murine brain to activate complement emerged around 7 days postpartum, correlating with the onset of myelin protein synthesis.

    • Conclusions:

    • Dimerized myelin basic protein (MBP) is a potent activator of the human complement system.
    • Complement activation by MBP may contribute to the pathogenesis of neurological disorders.
    • The developmental timing of complement activation in the brain aligns with myelin formation.