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Updated: Jul 26, 2025

Evaluation of the Interplay Between the Complement Protein C1q and Hyaluronic Acid in Promoting Cell Adhesion
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Complement component C1q is an immunological rheostat that regulates Fc:Fc R interactions.

Edward C So1, Hua Zhou1, Ariana Greenwell1

  • 1Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.

Immunogenetics
|June 15, 2023
PubMed
Summary

Complement factor C1q binding to immune complexes (ICs) transiently inhibits their interaction with Fc gamma receptors (FcγRs) on NK cells. This C1q-mediated blockade regulates immune cell activation and antibody-dependent cell-mediated cytotoxicity (ADCC).

Keywords:
AntibodyC1qComplementFc receptoprIgGImmune complex

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Area of Science:

  • Immunology
  • Complement System
  • Cellular Immunology

Background:

  • Immunoglobulin G (IgG) molecules possess overlapping binding sites for complement factor C1q and fragment crystallizable (Fc) gamma receptors (FcγRs).
  • The influence of C1q decoration on immune complexes (ICs) regarding their FcγR engagement is not well understood.

Purpose of the Study:

  • To investigate how C1q binding to ICs affects their interaction with FcγRs.
  • To elucidate the functional consequences of C1q-mediated modulation of FcγR engagement on immune cells.

Main Methods:

  • Utilized recombinant human Fc multimers as stable IC mimics.
  • Assessed C1q's effect on the interaction between IC mimics and FcγRIII (CD16) on human natural killer (NK) cells.
  • Evaluated NK cell functional responses, including 4-1BB upregulation and antibody-dependent cell-mediated cytotoxicity (ADCC).

Main Results:

  • C1q engagement with ICs directly and transiently inhibits their interaction with FcγRIII (CD16) on NK cells.
  • This inhibitory effect is dependent on IC size and the concentrations of C1q and Fc multimers.
  • C1q-mediated Fc blockade limits NK cell-induced 4-1BB upregulation and ADCC.

Conclusions:

  • C1q acts as an "immunologic rheostat," buffering FcγR-mediated activation of immune cells by circulating ICs.
  • C1q plays a novel regulatory role in immune homeostasis.
  • Complement factors exhibit pleiotropic effects beyond traditional effector functions.