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Complement component C1q is an immunological rheostat that regulates Fc:Fc\(\gamma\)R interactions

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Abstract

Though binding sites for the complement factor C1q and the canonical fragment crystallizable (Fc) gamma receptors (Fc\(\gamma\)Rs) on immunoglobulin G (IgG) molecules overlap, how C1q decoration of immune complexes (ICs) influences their ability to engage Fc\(\gamma\)Rs remains unknown. In this report, we use recombinant human Fc multimers as stable IC mimics to show that C1q engagement of ICs directly and transiently inhibits their interactions with Fc\(\gamma\)RIII (CD16) on human natural killer (NK) cells. This inhibition occurs by C1q engagement alone as well as in concert with other serum factors. Furthermore, the inhibition of Fc\(\gamma\)RIII engagement mediated by avid binding of C1q to ICs is directly associated with IC size and dependent on the concentrations of both C1q and Fc multimers present. Functionally, C1q-mediated Fc blockade limits the ability of NK cells to induce the upregulation of the cosignaling molecule, 4-1BB (CD137), and to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). Although C1q is traditionally viewed as a soluble effector molecule, we demonstrate that C1q may also take on the role of an “immunologic rheostat,” buffering Fc\(\gamma\)R-mediated activation of immune cells by circulating ICs. These data define a novel role for C1q as a regulator of immune homeostasis and add to our growing understanding that complement factors mediate pleiotropic effects.

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The data described in this manuscript is available upon request with the corresponding author.

References

  • Bayly-Jones C, Bubeck D, Dunstone MA (2017) The mystery behind membrane insertion: a review of the complement membrane attack complex. Philos Trans R Soc Lond B Biol Sci 372:20160221

    Google Scholar 

  • Bologna L, Gotti E, Da Roit F, Intermesoli T, Rambaldi A, Introna M, Golay J (2013) Ofatumumab is more efficient than rituximab in lysing B chronic lymphocytic leukemia cells in whole blood and in combination with chemotherapy. J Immunol 190:231–239

    CAS  PubMed  Google Scholar 

  • Botto M, Dell’Agnola C, Bygrave AE, Thompson EM, Cook HT, Petry F, Loos M, Pandolfi PP, Walport MJ (1998) Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat Genet 19:56–59

    CAS  PubMed  Google Scholar 

  • Botto M, Walport MJ (2002) C1q, Autoimmunity and Apoptosis. Immunobiology 205:395–406

    CAS  PubMed  Google Scholar 

  • Bruhns P (2012) Properties of mouse and human IgG receptors and their contribution to disease models 119:5640–5649

    CAS  Google Scholar 

  • Bruhns P, Iannascoli B, England P, Mancardi DA, Fernandez N, Jorieux S, Daëron M (2009) Specificity and affinity of human Fcγ receptors and their polymorphic variants for human IgG subclasses. Blood 113:3716–3725

    CAS  PubMed  Google Scholar 

  • Calcott MA, Muller-Eberhard HJ (1972) C1q protein of human complement. Biochemistry 11:3443–3450

    CAS  PubMed  Google Scholar 

  • Carroll MC (2004) A protective role for innate immunity in systemic lupus erythematosus. Nat Rev Immunol 4:825–831

    CAS  PubMed  Google Scholar 

  • Clynes R (2005) Immune complexes as therapy for autoimmunity. J Clin Investig 115:25–27

    CAS  PubMed  PubMed Central  Google Scholar 

  • Diebolder CA, Beurskens FJ, de Jong RN, Koning RI, Strumane K, Lindorfer MA, Voorhorst M, Ugurlar D, Rosati S, Heck AJ, van de Winkel JG, Wilson IA, Koster AJ, Taylor RP, Saphire EO, Burton DR, Schuurman J, Gros P, Parren PW (2014) Complement is activated by IgG hexamers assembled at the cell surface. Science 343:1260–1263

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fitzpatrick EA, Wang J, Strome SE (2020) Engineering of Fc Multimers as a Protein Therapy for Autoimmune Disease. Front Immunol 11:496

    CAS  PubMed  PubMed Central  Google Scholar 

  • Flajnik MF, Kasahara M (2001) Comparative Genomics of the MHC: Glimpses into the Evolution of the Adaptive Immune System. Immunity 15:351–362

    CAS  PubMed  Google Scholar 

  • Fraser DA, Bohlson SS, Jasinskiene N, Rawal N, Palmarini G, Ruiz S, Rochford R, Tenner AJ (2006) C1q and MBL, components of the innate immune system, influence monocyte cytokine expression. J Leukoc Biol 80:107–116

    CAS  PubMed  Google Scholar 

  • Gaboriaud C, Frachet P, Thielens NM, Arlaud GJ (2012) The Human C1q Globular Domain: Structure and Recognition of Non-Immune Self Ligands. Front Immunol 2

  • Gadjeva MG, Rouseva MM, Zlatarova AS, Reid KBM, Kishore U, Kojouharova MS (2008) Interaction of Human C1q with IgG and IgM: Revisited. Biochemistry 47:13093–13102

    CAS  PubMed  Google Scholar 

  • Galeotti C, Kaveri SV, Bayry J (2017) IVIG-mediated effector functions in autoimmune and inflammatory diseases. Int Immunol 29:491–498

    CAS  PubMed  Google Scholar 

  • Ghebrehiwet B, Habicht GS, Beck G (1990) Interaction of C1q with its receptor on cultured cell lines induces an anti-proliferative response. Clin Immunol Immunopathol 54:148–160

    CAS  PubMed  Google Scholar 

  • Ghebrehiwet B, Hosszu KK, Valentino A, Peerschke EI (2012) The C1q family of proteins: insights into the emerging non-traditional functions. Front Immunol 3

  • Golan MD, Burger R, Loos M (1982) Conformational changes in C1q after binding to immune complexes: detection of neoantigens with monoclonal antibodies. J Immunol 129:445–447

    CAS  PubMed  Google Scholar 

  • Heinz HP (1989) Biological functions of C1q expressed by conformational changes. Behring Institute Mitteilungen 20–31

  • Holers VM (2014) Complement and its receptors: new insights into human disease. Annu Rev Immunol 32:433–459

    CAS  PubMed  Google Scholar 

  • Idusogie EE, Presta LG, Gazzano-Santoro H, Totpal K, Wong PY, Ultsch M, Meng YG, Mulkerrin MG (2000) Mapping of the C1q binding site on rituxan, a chimeric antibody with a human IgG1 Fc. J Immunol 164:4178–4184

    CAS  PubMed  Google Scholar 

  • Jain A, Poonia B, So EC, Vyzasatya R, Burch EE, Olsen HS, Merigeon EY, Block DS, Zhang X, Schulze DH, Hanna NN, Twadell WS, Yfantis HG, Chan SL, Cai L, Strome SE (2013) Tumour antigen targeted monoclonal antibodies incorporating a novel multimerisation domain significantly enhance antibody dependent cellular cytotoxicity against colon cancer. Eur J Cancer 49:3344–3352

    CAS  PubMed  Google Scholar 

  • Kirschfink M, Mollnes TE (2003) Modern complement analysis. Clin Diagn Lab Immunol 10:982–989

    CAS  PubMed  PubMed Central  Google Scholar 

  • Klickstein LB, Barbashov SF, Liu T, Jack RM, Nicholson-Weller A (1997) Complement Receptor Type 1 (CR1, CD35) Is a Receptor for C1q. Immunity 7:345–355

    CAS  PubMed  Google Scholar 

  • Korb LC, Ahearn JM (1997) C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes: complement deficiency and systemic lupus erythematosus revisited. J Immunol 158:4525–4528

    CAS  PubMed  Google Scholar 

  • Lanier LL, Ruitenberg JJ, Phillips JH (1988) Functional and biochemical analysis of CD16 antigen on natural killer cells and granulocytes. J Immunol 141:3478–3485

    CAS  PubMed  Google Scholar 

  • Liang M, Schwickart M, Schneider AK, Vainshtein I, Del Nagro C, Standifer N, Roskos LK (2016) Receptor occupancy assessment by flow cytometry as a pharmacodynamic biomarker in biopharmaceutical development. Cytometry B Clin Cytom 90:117–127

    PubMed  Google Scholar 

  • Lin W, Voskens CJ, Zhang X, Schindler DG, Wood A, Burch E, Wei Y, Chen L, Tian G, Tamada K, Wang LX et al (2008) Fc dependent expression of CD137 on human NK cells: insights into "agonistic" effects of anti-CD137 monoclonal antibodies. Blood blood-2007–2011–122465

  • Lood C, Gullstrand B, Truedsson L, Olin AI, Alm GV, Ronnblom L, Sturfelt G, Eloranta ML, Bengtsson AA (2009) C1q inhibits immune complex-induced interferon-alpha production in plasmacytoid dendritic cells: a novel link between C1q deficiency and systemic lupus erythematosus pathogenesis. Arthritis Rheum 60:3081–3090

    CAS  PubMed  Google Scholar 

  • Lyu X, Zhao Q, Hui J, Wang T, Lin M, Wang K, Zhang J, Shentu J, Dalby PA, Zhang H, Liu B (2022) The global landscape of approved antibody therapies. Antibody therapeutics 5:233–257

    CAS  PubMed  PubMed Central  Google Scholar 

  • Macedo AC, Isaac L (2016) Systemic Lupus Erythematosus and Deficiencies of Early Components of the Complement Classical Pathway. Front Immunol 7:55

    PubMed  PubMed Central  Google Scholar 

  • Mollnes TE, Garred P, Bergseth G (1988) Effect of time, temperature and anticoagulants on in vitro complement activation: consequences for collection and preservation of samples to be examined for complement activation. Clin Exp Immunol 73:484–488

    CAS  PubMed  PubMed Central  Google Scholar 

  • Meyaard L, Adema GJ, Chang C, Woollatt E, Sutherland GR, Lanier LL, Phillips JH (1997) LAIR-1, a novel inhibitory receptor expressed on human mononuclear leukocytes. Immunity 7:283–290

    CAS  PubMed  Google Scholar 

  • Nonaka M, Kimura A (2006) Genomic view of the evolution of the complement system. Immunogenetics 58:701–713

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pickering MC, Walport MJ (2000) Links between complement abnormalities and systemic lupus erythematosus. Rheumatology 39:133–141

    CAS  PubMed  Google Scholar 

  • Pincetic A, Bournazos S, DiLillo DJ, Maamary J, Wang TT, Dahan R, Fiebiger BM, Ravetch JV (2014) Type I and type II Fc receptors regulate innate and adaptive immunity. Nat Immunol 15:707–716

    CAS  PubMed  PubMed Central  Google Scholar 

  • Psychogios N, Hau DD, Peng J, Guo AC, Mandal R, Bouatra S, Sinelnikov I, Krishnamurthy R, Eisner R, Gautam B, Young N, Xia J, Knox C, Dong E, Huang P, Hollander Z, Pedersen TL, Smith SR, Bamforth F, Greiner R, McManus B, Newman JW, Goodfriend T, Wishart DS (2011) The human serum metabolome PloS one 6:e16957

    CAS  PubMed  Google Scholar 

  • Reid KBM (2018) Complement Component C1q: Historical Perspective of a Functionally Versatile, and Structurally Unusual, Serum Protein. Front Immunol 9

  • Ricklin D, Reis ES, Lambris JD (2016) Complement in disease: a defence system turning offensive. Nat Rev Nephrol 12:383–401

    CAS  PubMed  PubMed Central  Google Scholar 

  • Roumenina LT, Sene D, Radanova M, Blouin J, Halbwachs-Mecarelli L, Dragon-Durey MA, Fridman WH, Fremeaux-Bacchi V (2011) Functional complement C1q abnormality leads to impaired immune complexes and apoptotic cell clearance. J Immunol 187:4369–4373

    CAS  PubMed  Google Scholar 

  • Schifferli JA, Ng YC, Peters DK (1986) The role of complement and its receptor in the elimination of immune complexes. N Engl J Med 315:488–495

    CAS  PubMed  Google Scholar 

  • Schmidt RE, Gessner JE (2005) Fc receptors and their interaction with complement in autoimmunity. Immunol Lett 100:56–67

    CAS  PubMed  Google Scholar 

  • Sellar GC, Blake DJ, Reid KB (1991) Characterization and organization of the genes encoding the A-, B- and C-chains of human complement subcomponent C1q. The complete derived amino acid sequence of human C1q. Biochem J 274( Pt 2):481–490.

  • Shchelokov D, Demin O Jr (2023) Receptor occupancy assessment and interpretation in terms of quantitative systems pharmacology: nivolumab case study. mAbs 15:2156317

  • Shields RL, Namenuk AK, Hong K, Meng YG, Rae J, Briggs J, Xie D, Lai J, Stadlen A, Li B, Fox JA, Presta LG (2001) High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R. J Biol Chem 276:6591–6604

    CAS  PubMed  Google Scholar 

  • Singh J, Ahmed A, Girardi G (2011) Role of complement component C1q in the onset of preeclampsia in mice. Hypertension 58:716–724

    CAS  PubMed  Google Scholar 

  • Slingsby JH, Norsworthy P, Pearce G, Vaishnaw AK, Issler H, Morley BJ, Walport MJ (1996) Homozygous hereditary C1q deficiency and systemic lupus erythematosus. A new family and the molecular basis of C1q deficiency in three families. Arthritis Rheum 39:663–670

    CAS  PubMed  Google Scholar 

  • So EC, Khaladj-Ghom A, Ji Y, Amin J, Song Y, Burch E, Zhou H, Sun H, Chen S, Bentzen S, Hertzano R, Zhang X, Strome SE (2019) NK cell expression of Tim-3: First impressions matter. Immunobiology 224:362–370

    CAS  PubMed  Google Scholar 

  • Son M, Santiago-Schwarz F, Al-Abed Y, Diamond B (2012) C1q limits dendritic cell differentiation and activation by engaging LAIR-1. Proc Natl Acad Sci U S A 109:E3160-3167

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sondermann P, Huber R, Oosthuizen V, Jacob U (2000) The 3.2-A crystal structure of the human IgG1 Fc fragment-Fc gammaRIII complex. Nature 406:267–273

    CAS  PubMed  Google Scholar 

  • Strome SE, Sausville EA, Mann D (2007) A Mechanistic Perspective of Monoclonal Antibodies in Cancer Therapy Beyond Target-Related Effects. Oncologist 12:1084–1095

    CAS  PubMed  Google Scholar 

  • Sun H, Olsen HS, Merigeon EY, So E, Burch E, Kinsey S, Papadimitriou JC, Drachenberg CB, Bentzen SM, Block DS, Strome SE, Zhang X (2017) Recombinant human IgG1 based Fc multimers, with limited FcR binding capacity, can effectively inhibit complement-mediated disease. J Autoimmun 84:97–108

    CAS  PubMed  Google Scholar 

  • Tan Y, Song D, Wu LH, Yu F, Zhao MH (2013) Serum levels and renal deposition of C1q complement component and its antibodies reflect disease activity of lupus nephritis. BMC Nephrol 14:63

    CAS  PubMed  PubMed Central  Google Scholar 

  • Taylor RJ, Chan SL, Wood A, Voskens CJ, Wolf JS, Lin W, Chapoval A, Schulze DH, Tian G, Strome SE (2009) FcgammaRIIIa polymorphisms and cetuximab induced cytotoxicity in squamous cell carcinoma of the head and neck. Cancer Immunol Immunother 58:997–1006

    CAS  PubMed  Google Scholar 

  • Teeling JL, Jansen-Hendriks T, Kuijpers TW, de Haas M, van de Winkel JGJ, Hack CE, Bleeker WK (2001) Therapeutic efficacy of intravenous immunoglobulin preparations depends on the immunoglobulin G dimers: studies in experimental immune thrombocytopenia. Blood 98:1095–1099

    CAS  PubMed  Google Scholar 

  • Thielens NM, Tedesco F, Bohlson SS, Gaboriaud C, Tenner AJ (2017) C1q: A fresh look upon an old molecule. Mol Immunol 89:73–83

    CAS  PubMed  PubMed Central  Google Scholar 

  • Walport MJ, Davies KA, Botto M (1998) C1q and Systemic Lupus Erythematosus. Immunobiology 199:265–285

    CAS  PubMed  Google Scholar 

  • Wang SY, Racila E, Taylor RP, Weiner GJ (2008) NK-cell activation and antibody-dependent cellular cytotoxicity induced by rituximab-coated target cells is inhibited by the C3b component of complement. Blood 111:1456–1463

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang SY, Veeramani S, Racila E, Cagley J, Fritzinger DC, Vogel CW, St John W, Weiner GJ (2009) Depletion of the C3 component of complement enhances the ability of rituximab-coated target cells to activate human NK cells and improves the efficacy of monoclonal antibody therapy in an in vivo model. Blood 114:5322–5330

    CAS  PubMed  PubMed Central  Google Scholar 

  • Young KR Jr, Ambrus JL Jr, Malbran A, Fauci AS, Tenner AJ (1991) Complement subcomponent C1q stimulates Ig production by human B lymphocytes. J Immunol 146:3356–3364

    CAS  PubMed  Google Scholar 

  • Zhang X, Owens J, Olsen HS, So E, Burch E, McCroskey MC, Li X, Weber GL, Bennett D, Rybin D, Zhou H, Hao EY, Mérigeon DS, Block G, LaRosa A, Strome SE (2019) A recombinant human IgG1 Fc multimer designed to mimic the active fraction of IVIG in autoimmunity. JCI Insight 4

  • Zhang X, Olsen HS, Chen S, So E, Zhou H, Burch E, Merigeon EY, Block DS, Strome SE (2016) Anti-CD20 Antibody with Multimerized Fc Domains: A Novel Strategy To Deplete B Cells and Augment Treatment of Autoimmune Disease. J Immunol 196:1165–1176

    CAS  PubMed  Google Scholar 

  • Zhou H, Olsen H, So E, Merigeon E, Rybin D, Owens J, LaRosa G, Block DS, Strome SE, Zhang X (2017) A fully recombinant human IgG1 Fc multimer (GL-2045) inhibits complement-mediated cytotoxicity and induces iC3b. Blood Adv 1:504–515

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

E.C.S. is a Ph.D. candidate at the University of Maryland, School of Medicine. This work is submitted in partial fulfillment of the requirement for the Ph.D. We would like to thank Dr. Elizabeth Fitzpatrick and Dr. Jane Owens for reviewing the manuscript. We would like to also thank Gliknik, Inc. for providing the GL-2045, G001, and G019 reagents.

Funding

This research was funded by the Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland SOM. GL-2045, G001, and G019 were provided, free of charge, by Gliknik, Inc.

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Author notes

  1. Xiaoyu Zhang and Scott E. Strome are co-last authors and contributed equally to this work.

Authors and Affiliations

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

    Edward C. So, Hua Zhou, Ariana Greenwell, Erin E. Burch, Yaping Ji & Xiaoyu Zhang

  2. Gliknik Inc., Baltimore, MD, USA

    Emmanuel Y. Mérigeon, Henrik S. Olsen & David S. Block

  3. Department of Epidemiology and Public Health, Division of Biostatistics and Bioinformatics, University of Maryland School of Medicine, Baltimore, MD, USA

    Søren M. Bentzen

  4. Department of Microbiology, Immunology, and Biochemistry, College of Medicine, University of Tennessee Health Science Center (UTHSC), 910 Madison Avenue, 10th floor Suite 1002, Memphis, TN, 38163, USA

    Scott E. Strome

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  1. Edward C. So
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Contributions

All authors made substantive intellectual contributions to the experimental design; E.C.S. and H.Z. performed the majority of the studies; E.C.S., H.Z., H.S.O., D.S.B., X.Z., and S.E.S. analyzed data and interpreted the studies; S.M.B. performed all statistical analyses; E.C.S., X.Z. and S.E.S. designed research; E.C.S., X.Z. and S.E.S. original draft preparation; E.C.S., H.S.O., D.S.B., X.Z., and S.E.S. review and editing; X.Z. and S.E.S. supervised the project; and all authors had input into the final version of the manuscript.

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Correspondence to Scott E. Strome.

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Conflict of interest disclosure

Dr. Scott E. Strome is a Cofounder, stockholder, and paid consultant for Gliknik Inc., a biotechnology company. He also serves on the SAB and holds stock options for Virion Inc. Finally, he receives significant royalties from the Mayo Clinic, for licensed IP surrounding the manipulation of the PD-1:PD-L1 pathway for the treatment of cancer.

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Supplemental Figure 1.

 A plate-based assay demonstrating the binding properties of GL-2045 or G019 (various concentrations) to immobilized C1q.

Supplemental Figure 2. A Assessment of C1q receptor expression on NK cells.Isolated NK cells were stained with various antibodies specific for different C1q receptors (LAIR1, LAIR2, cC1qR, gC1qR, and CR1) and the expression was determined by flow cytometry. B Various concentrations of human C1q (0, 5, 20, and 100 µg/ml) were cultured with human NK cells in order to assess C1q binding. An anti-C1q antibody was used to evaluate the levels of C1q binding by FACS. 

Supplemental Figure 3. A Isolated NK cells were incubated with culture media only, mIgG1 (10 µg/ml), or anti-CD16 (10 µg/ml) prior to the addition of DyLight 488 labeled G019 (1 µg/ml). Binding of G019 to NK cells was determined by flow cytometry. Data are shown from a representative sample (top panel) and summarized MFI (mean ± SEM) from three experiments (bottom panel). B FcγRIIA- or FcγRIIB-expressing CHO cells were incubated with Dylight 488 labeled GL-2045 in the presence or absence of recombinant human C1q (100 µg/ml). Binding of GL-2045 to CHO cell lines was determined by flow cytometry. Data are shown from a representative experiment (left panels) and as the summarized MFI (mean ± SEM) from three experiments (right panels). *p < 0.05, **p < 0.01. (PPTX 224 KB)

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So, E.C., Zhou, H., Greenwell, A. et al. Complement component C1q is an immunological rheostat that regulates Fc:Fc\(\gamma\)R interactions. Immunogenetics 75, 369–383 (2023). https://doi.org/10.1007/s00251-023-01311-x

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