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Complement activation by cross-linked B cell-membrane IgM

K Ohishi1, M Kanoh, H Shinomiya

  • 1Department of Microbiology, Ehime University School of Medicine, Japan.

Journal of Immunology (Baltimore, Md. : 1950)
|April 1, 1995
PubMed
Summary
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Cross-linked membrane IgM (mIgM) on B cells can activate the complement system. This process involves the classical complement pathway, leading to C3 deposition on the cell surface.

Area of Science:

  • Immunology
  • Complement System Biology

Background:

  • B cell membrane IgM (mIgM) is typically monomeric and does not activate complement.
  • Polymeric forms of IgM, like secreted IgM, are known to activate complement.
  • The ability of cross-linked mIgM to activate complement via the classical pathway was investigated.

Purpose of the Study:

  • To determine if cross-linked membrane IgM (mIgM) can activate the complement system.
  • To elucidate the mechanism of mIgM-mediated complement activation.

Main Methods:

  • Utilized CR2-deficient Ramos and mIgM(kappa)+, mIgD(kappa)+ P32 lymphoma cells.
  • Induced mIgM cross-linking using F(ab')2 antibodies against specific immunoglobulin chains (lambda, kappa, mu).
  • Assessed complement activation by measuring C3 deposition via flow cytometry and C1q binding.

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Main Results:

  • Cross-linking of mIgM on B cells induced significant C3 deposition in a classical complement pathway-dependent manner.
  • C3 deposition was dependent on C1q binding to cross-linked mIgM, but not Factor B or D.
  • Monoclonal Fab' fragments targeting mIgM inhibited C1 binding and subsequent complement activation.

Conclusions:

  • Cross-linked membrane IgM (mIgM) effectively triggers the classical pathway of complement activation.
  • This finding highlights a mechanism for complement activation directly by B cell surface immunoglobulin.
  • The study demonstrates that mIgM cross-linking leads to C3 deposition associated with mIgM.