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A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies
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FcµR and IgM-Mediated Complement Activation Cooperate to Enhance Humoral Immunity.

Zichao Wen1, Lulu Dong1, Jun Liu1

  • 1Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

European Journal of Immunology
|December 19, 2025
PubMed
Summary

Secretory IgM enhances IgG responses via two pathways: FcµR engagement and complement activation. These distinct, synergistic mechanisms are crucial for B cell activation, germinal center formation, and antibody production.

Keywords:
FcµRIgMcomplement activationgerminal center formationhumoral immune response

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Secretory IgM is vital for robust antigen-specific IgG responses.
  • Mechanisms of IgM's immune-enhancing effects, particularly Fc receptor (FcµR) engagement and complement activation, are not fully understood.
  • The interplay and redundancy between FcµR and complement pathways in B cell differentiation remain unclear.

Purpose of the Study:

  • To elucidate the distinct and cooperative roles of FcµR and complement pathways in IgM-mediated humoral immunity.
  • To investigate the functions of these pathways at different stages of B cell differentiation.
  • To define the molecular mechanisms by which IgM enhances B cell responses in vivo.

Main Methods:

  • Utilized FcµR-deficient mice and Cµ13 mice with complement-inactivating IgM.
  • Generated FcµR-/-Cµ13 double-mutant mice to assess combined pathway deficiencies.
  • Analyzed T-dependent immune responses, B cell activation, germinal center formation, and plasma cell differentiation.

Main Results:

  • FcµR and complement pathways play nonredundant, synergistic roles in IgG production.
  • Both pathways are essential for early B cell activation, expansion, class switch recombination, germinal center formation, and plasma cell differentiation.
  • Complement activation is critical for germinal center B cell proliferation and affinity maturation, while FcµR enhances naive B cell receptor signaling.

Conclusions:

  • Two distinct, cooperative IgM-mediated mechanisms involving FcµR and complement regulate humoral immunity.
  • FcµR signaling enhances naive B cell activation, whereas complement activation drives germinal center responses.
  • These findings clarify how IgM orchestrates B cell differentiation and antibody production through synergistic pathways.