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Related Experiment Videos

Complement activation in human lymphoid germinal centres.

J Zwirner1, E Felber, P Schmidt

  • 1Institut für Immunologie, Universität München, FRG.

Immunology
|February 1, 1989
PubMed
Summary

Complement activation products, including the membrane attack complex (MAC), are present in human lymphoid germinal centers. This indicates a close relationship between germinal centers and the complete complement cascade during normal immune responses.

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Area of Science:

  • Immunology
  • Complement System Biology

Background:

  • The role of complement activation products in normal human lymphatic tissue, specifically germinal centers, is not fully understood.
  • Germinal centers are crucial sites for immune regulation and B cell maturation.

Purpose of the Study:

  • To investigate the presence and distribution of complement activation products within morphologically normal human lymphatic tissues.
  • To elucidate the involvement of the complete complement cascade, including the membrane attack complex (MAC), in germinal centers.

Main Methods:

  • Utilized newly established monoclonal antibodies (mAbs) against C4 cleavage fragments (C4a, C4b, C4c, C4d).
  • Applied indirect immunoperoxidase staining on cryostat sections of tonsil, spleen, and lymph node tissues.
  • Investigated the complete complement activation sequence using antibodies against C1, C2, C3, factor B, C5, C9, C5b-9 neoantigens, and regulatory proteins (C4bp, factor I, factor H, properdin).

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Main Results:

  • C4d activation product was detected in germinal centers of all secondary lymphoid follicles across different organs.
  • C3d antigens were strongly localized to germinal centers, mirroring C4d distribution.
  • Components of the membrane attack complex (MAC), C5b-9, were found in germinal centers with weaker intensity.
  • Simultaneous deposition of C1, C4b, and C4 binding protein (C4bp) in some germinal centers suggests classical pathway activation.
  • Concomitant IgM deposition points to IgM-antigen complexes on follicular dendritic cells (FDC) as likely classical pathway activators.

Conclusions:

  • Human lymphoid germinal centers are sites where the complete complement activation cascade, including the MAC, is actively involved.
  • Complement activation in germinal centers is likely initiated via the classical pathway, possibly by IgM-antigen complexes.
  • These findings highlight the intricate interplay between germinal centers and the complement system in normal immune responses.