Natural antibody and complement-mediated antigen processing and presentation by B lymphocytes

B P Thornton1, V Vĕtvicka, G D Ross

  • 1Department of Microbiology and Immunology, University of Louisville, KY 40292.

Insights

Natural antibodies and complement C3 facilitate immune complex processing by B cells. This process involves complement C3dg, B cell receptors CR2 and FcRII, and enhances T cell activation.

Area of Science:

  • Immunology
  • Biochemistry

Background:

  • Normal immune responses to novel protein antigens require complement C3 and its receptor CR2 (CD21).
  • Natural antibodies are crucial for initiating immune responses against previously unencountered antigens.

Purpose of the Study:

  • To investigate if natural antibodies against keyhole limpet hemocyanin (KLH) form immune complexes (ICs) that activate complement and promote B cell antigen processing via CR2.
  • To elucidate the roles of complement fragments (iC3b/C3dg) and B cell receptors (CR1, CR2, CR3, FcRII) in antigen processing and presentation.

Main Methods:

  • Detection of anti-KLH IgM and IgG in normal human sera.
  • Formation and characterization of immune complexes (ICs) with complement components.
  • Assessment of KLH processing and presentation by B cell clones using flow cytometry and blocking assays.
  • Analysis of co-stimulatory molecule (CD80) expression on B cells.

Main Results:

  • Natural IgM and IgG anti-KLH antibodies were detected, forming ICs that bound to B cells via complement (iC3b/C3dg) and receptors CR1, CR2, and CR3.
  • Complement fragment C3dg mediated KLH IC binding to CR2 on B cells, facilitating antigen processing.
  • B cell antigen processing and presentation to T cells were enhanced by KLH-specific B cells and involved CR2 and FcRII.
  • Binding of KLH ICs induced B7/BB1 (CD80) expression on B cells, dependent on IgG binding to FcRII (CD32).

Conclusions:

  • Responses to primary protein antigens involve natural IgG antibodies and complement C3.
  • B cell antigen processing and presentation are mediated by CR2 and FcRII interactions with immune complexes.
  • This pathway is critical for initiating adaptive immune responses to novel protein antigens.

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