Complement component C1q is an immunological rheostat that regulates Fc:Fc R interactions.

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.