Distinct Antibody Fc-profiles in Lymph During Homeostasis and Chronic HIV Infection

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Published: Feb 23, 2026
DOI: https://doi.org/10.20411/pai.v11i1.887
Keywords:
Antibodies, Compartmentalization, Fc-receptors, HIV, Isotype, Lymph, Tissues

Main Article Content

Ryan P. McNamara
Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts
Audrey L. Butler
Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts
Sepideh Dolatshahi
Ragon Institute of MGH, MIT and Harvard; Massachusetts Institute of Technology, Cambridge, Massachusetts
Sabian Taylor
Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts
Yoav Dori
Division of Cardiology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
Ian Frank
Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Maxim G. Itkin
Center for Lymphatic Disorders, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Michael R. Betts
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Galit Alter
Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts

Abstract

Background: Antibodies play a critical role in the control of pathogens and tumors through their ability to recognize non-self and then direct immune-mediated destruction. Antibodies are generated by plasma cells or plasmablasts, located throughout the tissues, and are transported between blood, lymph, mucosal secretions, and tissues to survey all sites for pathogens or malignant cells. However, mounting evidence suggests antibodies that transit across compartments (from the blood to the brain, mucosal tissues, or placenta) differ from those in systemic circulation. Whether antibodies also differ as they transit from the blood into non-privileged tissues remains unclear. Thus, here we aimed to define the landscape of antibodies that exist within the blood and tissues and begin to define the properties that lead to antibody transfer across compartments. 


Methods: To analyze tissue antibodies, we performed antibody profiling in chyle, a fluid component of lymph collected via the thoracic duct, contrasting these profiles to matched plasma samples. 


Results: Equivalent levels of pathogen-specific IgG antibodies and functions were observed across the plasma and lymph in people without HIV. However, this balance in IgG transfer was disrupted in people living with HIV, with significantly lower transfer ratios across several pathogen-specific IgG subpopulations in chyle. 


Conclusion: Differential transfer of IgG was Fc-receptor dependent, pointing to a mechanism of transfer into tissues during inflammatory disease that may have a critical role in selecting the antibodies able to access the peripheral and lymphoid tissues.

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References

1. Dalessandri T, Strid J. Beneficial autoimmunity at body surfaces - immune surveillance and rapid type 2 immunity regulate tissue homeostasis and cancer. Front Immunol. 2014;5:347. doi: 10.3389/fimmu.2014.00347. PubMed PMID: 25101088; PMCID: PMC4105846.

DOI: https://doi.org/10.3389/fimmu.2014.00347

2. Thom G, Hatcher J, Hearn A, Paterson J, Rodrigo N, Beljean A, Gurrell I, Webster C. Isolation of blood-brain barrier-crossing antibodies from a phage display library by competitive elution and their ability to penetrate the central nervous system. MAbs. 2018;10(2):304-14. doi: 10.1080/19420862.2017.1409320. PubMed PMID: 29182455; PMCID: PMC5825204.

DOI: https://doi.org/10.1080/19420862.2017.1409320

3. Sun Z, Fu YX, Peng H. Targeting tumor cells with antibodies enhances anti-tumor immunity. Biophys Rep. 2018;4(5):243-53. doi: 10.1007/s41048-018-0070-2. PubMed PMID: 30533489; PMCID: PMC6245233.

DOI: https://doi.org/10.1007/s41048-018-0070-2

4. Mantis NJ, Rol N, Corthesy B. Secretory IgA’s complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunol. 2011;4(6):603-11. doi: 10.1038/mi.2011.41. PubMed PMID: 21975936; PMCID: PMC3774538.

DOI: https://doi.org/10.1038/mi.2011.41

5. Shekhar S, Schenck K, Petersen FC. Exploring Host-Commensal Interactions in the Respiratory Tract. Front Immunol. 2017;8:1971. doi: 10.3389/fimmu.2017.01971. PubMed PMID: 29387057; PMCID: PMC5776090.

6. Hjelm F, Carlsson F, Getahun A, Heyman B. Antibody-mediated regulation of the immune response. Scand J Immunol. 2006;64(3):177-84. doi: 10.1111/j.1365-3083.2006.01818.x. PubMed PMID: 16918684.

DOI: https://doi.org/10.1111/j.1365-3083.2006.01818.x

7. Spiekermann GM, Finn PW, Ward ES, Dumont J, Dickinson BL, Blumberg RS, Lencer WI. Receptor-mediated immunoglobulin G transport across mucosal barriers in adult life: functional expression of FcRn in the mammalian lung. J Exp Med. 2002;196(3):303-10. doi: 10.1084/jem.20020400. PubMed PMID: 12163559; PMCID: PMC2193935.

DOI: https://doi.org/10.1084/jem.20020400

8. Ryman JT, Meibohm B. Pharmacokinetics of Monoclonal Antibodies. CPT Pharmacometrics Syst Pharmacol. 2017;6(9):576-88. doi: 10.1002/psp4.12224. PubMed PMID: 28653357; PMCID: PMC5613179.

DOI: https://doi.org/10.1002/psp4.12224

9. Tabrizi M, Bornstein GG, Suria H. Biodistribution mechanisms of therapeutic monoclonal antibodies in health and disease. AAPS J. 2010;12(1):33-43. doi: 10.1208/s12248-009-9157-5. PubMed PMID: 19924542; PMCID: PMC2811642.

DOI: https://doi.org/10.1208/s12248-009-9157-5

10. Jones AT, Shen X, Walter KL, LaBranche CC, Wyatt LS, Tomaras GD, Montefiori DC, Moss B, Barouch DH, Clements JD, Kozlowski PA, Varadarajan R, Amara RR. HIV-1 vaccination by needle-free oral injection induces strong mucosal immunity and protects against SHIV challenge. Nature communications. 2019;10(1):798. doi: 10.1038/s41467-019-08739-4. PubMed PMID: 30778066; PMCID: PMC6379385.

DOI: https://doi.org/10.1038/s41467-019-08739-4

11. Brimberg L, Mader S, Fujieda Y, Arinuma Y, Kowal C, Volpe BT, Diamond B. Antibodies as Mediators of Brain Pathology. Trends in immunology. 2015;36(11):709-24. doi: 10.1016/j.it.2015.09.008. PubMed PMID: 26494046; PMCID: PMC4907328.

DOI: https://doi.org/10.1016/j.it.2015.09.008

12. Jennewein MF, Goldfarb I, Dolatshahi S, Cosgrove C, Noelette FJ, Krykbaeva M, Das J, Sarkar A, Gorman MJ, Fischinger S, Boudreau CM, Brown J, Cooperrider JH, Aneja J, Suscovich TJ, Graham BS, Lauer GM, Goetghebuer T, Marchant A, Lauffenburger D, Kim AY, Riley LE, Alter G. Fc Glycan-Mediated Regulation of Placental Antibody Transfer. Cell. 2019;178(1):202-15 e14. doi: 10.1016/j.cell.2019.05.044. PubMed PMID: 31204102; PMCID: PMC6741440.

DOI: https://doi.org/10.1016/j.cell.2019.05.044

13. Kumar BV, Ma W, Miron M, Granot T, Guyer RS, Carpenter DJ, Senda T, Sun X, Ho SH, Lerner H, Friedman AL, Shen Y, Farber DL. Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites. Cell Rep. 2017;20(12):2921-34. doi: 10.1016/j.celrep.2017.08.078. PubMed PMID: 28930685; PMCID: PMC5646692.

DOI: https://doi.org/10.1016/j.celrep.2017.08.078

14. Topham DJ, Reilly EC. Tissue-Resident Memory CD8(+) T Cells: From Phenotype to Function. Front Immunol. 2018;9:515. doi: 10.3389/fimmu.2018.00515. PubMed PMID: 29632527; PMCID: PMC5879098.

DOI: https://doi.org/10.3389/fimmu.2018.00515

15. Buggert M, Vella LA, Nguyen S, Wu VH, Chen Z, Sekine T, Perez-Potti A, Maldini CR, Manne S, Darko S, Ransier A, Kuri-Cervantes L, Japp AS, Brody IB, Ivarsson MA, Gorin JB, Rivera-Ballesteros O, Hertwig L, Antel JP, Johnson ME, Okoye A, Picker L, Vahedi G, Sparrelid E, Llewellyn-Lacey S, Gostick E, Sandberg JK, Bjorkstrom N, Bar-Or A, Dori Y, Naji A, Canaday DH, Laufer TM, Wells AD, Price DA, Frank I, Douek DC, Wherry EJ, Itkin MG, Betts MR. The Identity of Human Tissue-Emigrant CD8(+) T Cells. Cell. 2020;183(7):1946-61 e15. doi: 10.1016/j.cell.2020.11.019. PubMed PMID: 33306960; PMCID: PMC9341432.

DOI: https://doi.org/10.1016/j.cell.2020.11.019

16. Mascelli MA, Zhou H, Sweet R, Getsy J, Davis HM, Graham M, Abernethy D. Molecular, biologic, and pharmacokinetic properties of monoclonal antibodies: impact of these parameters on early clinical development. Journal of clinical pharmacology. 2007;47(5):553-65. doi: 10.1177/0091270006298360. PubMed PMID: 17379759.

DOI: https://doi.org/10.1177/0091270006298360

17. Xu Z, Vu T, Lee H, Hu C, Ling J, Yan H, Baker D, Beutler A, Pendley C, Wagner C, Davis HM, Zhou H. Population pharmacokinetics of golimumab, an anti-tumor necrosis factor-alpha human monoclonal antibody, in patients with psoriatic arthritis. Journal of clinical pharmacology. 2009;49(9):1056-70. doi: 10.1177/0091270009339192. PubMed PMID: 19617465.

DOI: https://doi.org/10.1177/0091270009339192

18. Lv S, Wang Q, Zhao W, Han L, Wang Q, Batchu N, Ulain Q, Zou J, Sun C, Du J, Song Q, Li Q. A review of the postoperative lymphatic leakage. Oncotarget. 2017;8(40):69062-75. doi: 10.18632/oncotarget.17297. PubMed PMID: 28978181; PMCID: PMC5620321.

DOI: https://doi.org/10.18632/oncotarget.17297

19. Delaney SW, Shi H, Shokrani A, Sinha UK. Management of Chyle Leak after Head and Neck Surgery: Review of Current Treatment Strategies. Int J Otolaryngol. 2017;2017:8362874. doi: 10.1155/2017/8362874. PubMed PMID: 28203252; PMCID: PMC5288539.

20. McGrath EE, Blades Z, Anderson PB. Chylothorax: aetiology, diagnosis and therapeutic options. Respir Med. 2010;104(1):1-8. doi: 10.1016/j.rmed.2009.08.010. PubMed PMID: 19766473.

DOI: https://doi.org/10.1016/j.rmed.2009.08.010

21. Haig DM, Hopkins J, Miller HR. Local immune responses in afferent and efferent lymph. Immunology. 1999;96(2):155-63. doi: 10.1046/j.1365-2567.1999.00681.x. PubMed PMID: 10233690; PMCID: PMC2326739.

DOI: https://doi.org/10.1046/j.1365-2567.1999.00681.x

22. Buggert M, Nguyen S, Salgado-Montes de Oca G, Bengsch B, Darko S, Ransier A, Roberts ER, Del Alcazar D, Brody IB, Vella LA, Beura L, Wijeyesinghe S, Herati RS, Del Rio Estrada PM, Ablanedo-Terrazas Y, Kuri-Cervantes L, Sada Japp A, Manne S, Vartanian S, Huffman A, Sandberg JK, Gostick E, Nadolski G, Silvestri G, Canaday DH, Price DA, Petrovas C, Su LF, Vahedi G, Dori Y, Frank I, Itkin MG, Wherry EJ, Deeks SG, Naji A, Reyes-Teran G, Masopust D, Douek DC, Betts MR. Identification and characterization of HIV-specific resident memory CD8(+) T cells in human lymphoid tissue. Sci Immunol. 2018;3(24). doi: 10.1126/sciimmunol.aar4526. PubMed PMID: 29858286; PMCID: PMC6357781.

DOI: https://doi.org/10.1126/sciimmunol.aar4526

23. Vella LA, Buggert M, Manne S, Herati RS, Sayin I, Kuri-Cervantes L, Bukh Brody I, O’Boyle KC, Kaprielian H, Giles JR, Nguyen S, Muselman A, Antel JP, Bar-Or A, Johnson ME, Canaday DH, Naji A, Ganusov VV, Laufer TM, Wells AD, Dori Y, Itkin MG, Betts MR, Wherry EJ. T follicular helper cells in human efferent lymph retain lymphoid characteristics. J Clin Invest. 2019;129(8):3185-200. doi: 10.1172/JCI125628. PubMed PMID: 31264971; PMCID: PMC6668682.

DOI: https://doi.org/10.1172/JCI125628

24. Voillet V, Buggert M, Slichter CK, Berkson JD, Mair F, Addison MM, Dori Y, Nadolski G, Itkin MG, Gottardo R, Betts MR, Prlic M. Human MAIT cells exit peripheral tissues and recirculate via lymph in steady state conditions. JCI Insight. 2018;3(7). doi: 10.1172/jci.insight.98487. PubMed PMID: 29618662; PMCID: PMC5928862.

DOI: https://doi.org/10.1172/jci.insight.98487

25. Brown EP, Dowell KG, Boesch AW, Normandin E, Mahan AE, Chu T, Barouch DH, Bailey-Kellogg C, Alter G, Ackerman ME. Multiplexed Fc array for evaluation of antigen-specific antibody effector profiles. J Immunol Methods. 2017;443:33-44. doi: 10.1016/j.jim.2017.01.010. PubMed PMID: 28163018; PMCID: PMC5333794.

DOI: https://doi.org/10.1016/j.jim.2017.01.010

26. Brown EP, Licht AF, Dugast AS, Choi I, Bailey-Kellogg C, Alter G, Ackerman ME. High-throughput, multiplexed IgG subclassing of antigen-specific antibodies from clinical samples. J Immunol Methods. 2012;386(1-2):117-23. doi: 10.1016/j.jim.2012.09.007. PubMed PMID: 23023091; PMCID: PMC3475184.

DOI: https://doi.org/10.1016/j.jim.2012.09.007

27. Bartsch YC, Tong X, Kang J, Avendano MJ, Serrano EF, Garcia-Salum T, Pardo-Roa C, Riquelme A, Cai Y, Renzi I, Stewart-Jones G, Chen B, Medina RA, Alter G. Omicron variant Spike-specific antibody binding and Fc activity are preserved in recipients of mRNA or inactivated COVID-19 vaccines. Sci Transl Med. 2022;14(642):eabn9243. doi: 10.1126/scitranslmed.abn9243. PubMed PMID: 35289637; PMCID: PMC8995028.

DOI: https://doi.org/10.1126/scitranslmed.abn9243

28. Ackerman ME, Moldt B, Wyatt RT, Dugast AS, McAndrew E, Tsoukas S, Jost S, Berger CT, Sciaranghella G, Liu Q, Irvine DJ, Burton DR, Alter G. A robust, high-throughput assay to determine the phagocytic activity of clinical antibody samples. J Immunol Methods. 2011;366(1-2):8-19. doi: 10.1016/j.jim.2010.12.016. PubMed PMID: 21192942; PMCID: PMC3050993.

DOI: https://doi.org/10.1016/j.jim.2010.12.016

29. Karsten CB, Mehta N, Shin SA, Diefenbach TJ, Slein MD, Karpinski W, Irvine EB, Broge T, Suscovich TJ, Alter G. A versatile high-throughput assay to characterize antibody-mediated neutrophil phagocytosis. J Immunol Methods. 2019;471:46-56. doi: 10.1016/j.jim.2019.05.006. PubMed PMID: 31132351; PMCID: PMC6620195.

DOI: https://doi.org/10.1016/j.jim.2019.05.006

30. Fischinger S, Fallon JK, Michell AR, Broge T, Suscovich TJ, Streeck H, Alter G. A high-throughput, bead-based, antigen-specific assay to assess the ability of antibodies to induce complement activation. J Immunol Methods. 2019;473:112630. doi: 10.1016/j.jim.2019.07.002. PubMed PMID: 31301278; PMCID: PMC6722412.

DOI: https://doi.org/10.1016/j.jim.2019.07.002

31. Vis DJ, Westerhuis JA, Hoefsloot HC, Pijl H, Roelfsema F, van der Greef J, Smilde AK. Endocrine pulse identification using penalized methods and a minimum set of assumptions. Am J Physiol Endocrinol Metab. 2010;298(2):E146-55. doi: 10.1152/ajpendo.00048.2009. PubMed PMID: 19861586.

DOI: https://doi.org/10.1152/ajpendo.00048.2009

32. Lee Y, Chung H, Arnold MA. Improving the robustness of a partial least squares (PLS) model based on pure component selectivity analysis and range optimization: case study for the analysis of an etching solution containing hydrogen peroxide. Anal Chim Acta. 2006;572(1):93-101. doi: 10.1016/j.aca.2006.05.019. PubMed PMID: 17723465.

DOI: https://doi.org/10.1016/j.aca.2006.05.019

33. Lau KS, Juchheim AM, Cavaliere KR, Philips SR, Lauffenburger DA, Haigis KM. In vivo systems analysis identifies spatial and temporal aspects of the modulation of TNF-alpha-induced apoptosis and proliferation by MAPKs. Sci Signal. 2011;4(165):ra16. doi: 10.1126/scisignal.2001338. PubMed PMID: 21427409; PMCID: PMC3963028.

DOI: https://doi.org/10.1126/scisignal.2001338

34. Horton RE, Vidarsson G. Antibodies and their receptors: different potential roles in mucosal defense. Front Immunol. 2013;4:200. doi: 10.3389/fimmu.2013.00200. PubMed PMID: 23882268; PMCID: PMC3712224.

35. Wilcox CR, Holder B, Jones CE. Factors Affecting the FcRn-Mediated Transplacental Transfer of Antibodies and Implications for Vaccination in Pregnancy. Front Immunol. 2017;8:1294. doi: 10.3389/fimmu.2017.01294. PubMed PMID: 29163461; PMCID: PMC5671757.

DOI: https://doi.org/10.3389/fimmu.2017.01294

36. Brandsma AM, Bondza S, Evers M, Koutstaal R, Nederend M, Jansen JHM, Rosner T, Valerius T, Leusen JHW, Ten Broeke T. Potent Fc Receptor Signaling by IgA Leads to Superior Killing of Cancer Cells by Neutrophils Compared to IgG. Front Immunol. 2019;10(704):704. doi: 10.3389/fimmu.2019.00704. PubMed PMID: 31031746; PMCID: PMC6470253.

DOI: https://doi.org/10.3389/fimmu.2019.00704

37. Zicari S, Sessa L, Cotugno N, Ruggiero A, Morrocchi E, Concato C, Rocca S, Zangari P, Manno EC, Palma P. Immune Activation, Inflammation, and Non-AIDS Co-Morbidities in HIV-Infected Patients under Long-Term ART. Viruses. 2019;11(3). doi: 10.3390/v11030200. PubMed PMID: 30818749; PMCID: PMC6466530.

DOI: https://doi.org/10.3390/v11030200

38. Jaworski JP, Cahn P. Preventive and therapeutic features of broadly neutralising monoclonal antibodies against HIV-1. The lancet HIV. 2018;5(12):e723-e31. doi: 10.1016/S2352-3018(18)30174-7. PubMed PMID: 30245003.

DOI: https://doi.org/10.1016/S2352-3018(18)30174-7

39. Walsh SR, Seaman MS. Broadly Neutralizing Antibodies for HIV-1 Prevention. Front Immunol. 2021;12:712122. doi: 10.3389/fimmu.2021.712122. PubMed PMID: 34354713; PMCID: PMC8329589.

DOI: https://doi.org/10.3389/fimmu.2021.712122

40. Bricault CA, Yusim K, Seaman MS, Yoon H, Theiler J, Giorgi EE, Wagh K, Theiler M, Hraber P, Macke JP, Kreider EF, Learn GH, Hahn BH, Scheid JF, Kovacs JM, Shields JL, Lavine CL, Ghantous F, Rist M, Bayne MG, Neubauer GH, McMahan K, Peng H, Cheneau C, Jones JJ, Zeng J, Ochsenbauer C, Nkolola JP, Stephenson KE, Chen B, Gnanakaran S, Bonsignori M, Williams LD, Haynes BF, Doria-Rose N, Mascola JR, Montefiori DC, Barouch DH, Korber B. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe. 2019;25(1):59-72 e8. doi: 10.1016/j.chom.2018.12.001. PubMed PMID: 30629920; PMCID: PMC6331341.

DOI: https://doi.org/10.1016/j.chom.2018.12.001

41. Wang P, Gajjar MR, Yu J, Padte NN, Gettie A, Blanchard JL, Russell-Lodrigue K, Liao LE, Perelson AS, Huang Y, Ho DD. Quantifying the contribution of Fc-mediated effector functions to the antiviral activity of anti-HIV-1 IgG1 antibodies in vivo. Proc Natl Acad Sci U S A. 2020;117(30):18002-9. doi: 10.1073/pnas.2008190117. PubMed PMID: 32665438; PMCID: PMC7395461.

DOI: https://doi.org/10.1073/pnas.2008190117

42. Liu J, Ghneim K, Sok D, Bosche WJ, Li Y, Chipriano E, Berkemeier B, Oswald K, Borducchi E, Cabral C, Peter L, Brinkman A, Shetty M, Jimenez J, Mondesir J, Lee B, Giglio P, Chandrashekar A, Abbink P, Colantonio A, Gittens C, Baker C, Wagner W, Lewis MG, Li W, Sekaly RP, Lifson JD, Burton DR, Barouch DH. Antibody-mediated protection against SHIV challenge includes systemic clearance of distal virus. Science. 2016;353(6303):1045-9. doi: 10.1126/science.aag0491. PubMed PMID: 27540005; PMCID: PMC5237379.

DOI: https://doi.org/10.1126/science.aag0491

43. Stephenson KE, Barouch DH. Broadly Neutralizing Antibodies for HIV Eradication. Curr HIV/AIDS Rep. 2016;13(1):31-7. doi: 10.1007/s11904-016-0299-7. PubMed PMID: 26841901; PMCID: PMC4779134.

DOI: https://doi.org/10.1007/s11904-016-0299-7

44. Mendoza P, Gruell H, Nogueira L, Pai JA, Butler AL, Millard K, Lehmann C, Suarez I, Oliveira TY, Lorenzi JCC, Cohen YZ, Wyen C, Kummerle T, Karagounis T, Lu CL, Handl L, Unson-O’Brien C, Patel R, Ruping C, Schlotz M, Witmer-Pack M, Shimeliovich I, Kremer G, Thomas E, Seaton KE, Horowitz J, West AP, Jr., Bjorkman PJ, Tomaras GD, Gulick RM, Pfeifer N, Fatkenheuer G, Seaman MS, Klein F, Caskey M, Nussenzweig MC. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature. 2018;561(7724):479-84. doi: 10.1038/s41586-018-0531-2. PubMed PMID: 30258136; PMCID: PMC6166473.

DOI: https://doi.org/10.1038/s41586-018-0531-2

45. Gaudinski MR, Houser KV, Doria-Rose NA, Chen GL, Rothwell RSS, Berkowitz N, Costner P, Holman LA, Gordon IJ, Hendel CS, Kaltovich F, Conan-Cibotti M, Gomez Lorenzo M, Carter C, Sitar S, Carlton K, Gall J, Laurencot C, Lin BC, Bailer RT, McDermott AB, Ko SY, Pegu A, Kwon YD, Kwong PD, Namboodiri AM, Pandey JP, Schwartz R, Arnold F, Hu Z, Zhang L, Huang Y, Koup RA, Capparelli EV, Graham BS, Mascola JR, Ledgerwood JE, team VRCs. Safety and pharmacokinetics of broadly neutralising human monoclonal antibody VRC07-523LS in healthy adults: a phase 1 dose-escalation clinical trial. The lancet HIV. 2019;6(10):e667-e79. doi: 10.1016/S2352-3018(19)30181-X. PubMed PMID: 31473167; PMCID: PMC11100866.

DOI: https://doi.org/10.1016/S2352-3018(19)30181-X

46. Caskey M. Broadly neutralizing antibodies for the treatment and prevention of HIV infection. Curr Opin HIV AIDS. 2020;15(1):49-55. doi: 10.1097/COH.0000000000000600. PubMed PMID: 31764199; PMCID: PMC7340121.

DOI: https://doi.org/10.1097/COH.0000000000000600

47. Caskey M, Klein F, Nussenzweig MC. Broadly neutralizing anti-HIV-1 monoclonal antibodies in the clinic. Nat Med. 2019;25(4):547-53. doi: 10.1038/s41591-019-0412-8. PubMed PMID: 30936546; PMCID: PMC7322694.

DOI: https://doi.org/10.1038/s41591-019-0412-8

48. Sumiyoshi K, Mokuno H, Iesaki T, Shimada K, Miyazaki T, Kume A, Kiyanagi T, Kuremoto K, Watanabe Y, Tada N, Daida H. Deletion of the Fc receptors gamma chain preserves endothelial function affected by hypercholesterolaemia in mice fed on a high-fat diet. Cardiovasc Res. 2008;80(3):463-70. doi: 10.1093/cvr/cvn206. PubMed PMID: 18694873.

DOI: https://doi.org/10.1093/cvr/cvn206

49. Karpanen T, Alitalo K. Lymphatic vessels as targets of tumor therapy? J Exp Med. 2001;194(6):F37-42. doi: 10.1084/jem.194.6.f37. PubMed PMID: 11561002; PMCID: PMC2195960.

DOI: https://doi.org/10.1084/jem.194.6.F37

50. Dahlberg AM, Kaminskas LM, Smith A, Nicolazzo JA, Porter CJ, Bulitta JB, McIntosh MP. The lymphatic system plays a major role in the intravenous and subcutaneous pharmacokinetics of trastuzumab in rats. Mol Pharm. 2014;11(2):496-504. doi: 10.1021/mp400464s. PubMed PMID: 24350780.

DOI: https://doi.org/10.1021/mp400464s

51. Wang TT, Ravetch JV. Functional diversification of IgGs through Fc glycosylation. J Clin Invest. 2019;129(9):3492-8. doi: 10.1172/JCI130029. PubMed PMID: 31478910; PMCID: PMC6715372.

DOI: https://doi.org/10.1172/JCI130029

52. Lu LL, Suscovich TJ, Fortune SM, Alter G. Beyond binding: antibody effector functions in infectious diseases. Nat Rev Immunol. 2018;18(1):46-61. doi: 10.1038/nri.2017.106. PubMed PMID: 29063907; PMCID: PMC6369690.

DOI: https://doi.org/10.1038/nri.2017.106

53. Kubagawa H, Honjo K, Ohkura N, Sakaguchi S, Radbruch A, Melchers F, Jani PK. Functional Roles of the IgM Fc Receptor in the Immune System. Front Immunol. 2019;10:945. doi: 10.3389/fimmu.2019.00945. PubMed PMID: 31130948; PMCID: PMC6509151.

DOI: https://doi.org/10.3389/fimmu.2019.00945

54. Atyeo C, Pullen KM, Bordt EA, Fischinger S, Burke J, Michell A, Slein MD, Loos C, Shook LL, Boatin AA, Yockey LJ, Pepin D, Meinsohn MC, Nguyen NMP, Chauvin M, Roberts D, Goldfarb IT, Matute JD, James KE, Yonker LM, Bebell LM, Kaimal AJ, Gray KJ, Lauffenburger D, Edlow AG, Alter G. Compromised SARS-CoV-2-specific placental antibody transfer. Cell. 2021;184(3):628-42 e10. doi: 10.1016/j.cell.2020.12.027. PubMed PMID: 33476549; PMCID: PMC7755577.

DOI: https://doi.org/10.1016/j.cell.2020.12.027

55. Pan L, Kreisle RA, Shi Y. Expression of endothelial cell IgG Fc receptors and markers on various cultures. Chin Med J (Engl). 1999;112(2):157-61. PubMed PMID: 11593585.

56. De Milito A, Nilsson A, Titanji K, Thorstensson R, Reizenstein E, Narita M, Grutzmeier S, Sonnerborg A, Chiodi F. Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection. Blood. 2004;103(6):2180-6. doi: 10.1182/blood-2003-07-2375. PubMed PMID: 14604962.

DOI: https://doi.org/10.1182/blood-2003-07-2375

57. Ackerman ME, Crispin M, Yu X, Baruah K, Boesch AW, Harvey DJ, Dugast AS, Heizen EL, Ercan A, Choi I, Streeck H, Nigrovic PA, Bailey-Kellogg C, Scanlan C, Alter G. Natural variation in Fc glycosylation of HIV-specific antibodies impacts antiviral activity. J Clin Invest. 2013;123(5):2183-92. doi: 10.1172/JCI65708. PubMed PMID: 23563315; PMCID: PMC3637034.

DOI: https://doi.org/10.1172/JCI65708

58. Kamburova EG, Koenen HJ, Borgman KJ, ten Berge IJ, Joosten I, Hilbrands LB. A single dose of rituximab does not deplete B cells in secondary lymphoid organs but alters phenotype and function. Am J Transplant. 2013;13(6):1503-11. doi: 10.1111/ajt.12220. PubMed PMID: 23570303.

DOI: https://doi.org/10.1111/ajt.12220

59. Huang H, Benoist C, Mathis D. Rituximab specifically depletes short-lived autoreactive plasma cells in a mouse model of inflammatory arthritis. Proc Natl Acad Sci U S A. 2010;107(10):4658-63. doi: 10.1073/pnas.1001074107. PubMed PMID: 20176942; PMCID: PMC2842072.

DOI: https://doi.org/10.1073/pnas.1001074107

60. Rath T, Kuo TT, Baker K, Qiao SW, Kobayashi K, Yoshida M, Roopenian D, Fiebiger E, Lencer WI, Blumberg RS. The immunologic functions of the neonatal Fc receptor for IgG. J Clin Immunol. 2013;33 Suppl 1(Suppl 1):S9-17. doi: 10.1007/s10875-012-9768-y. PubMed PMID: 22948741; PMCID: PMC3548031.

DOI: https://doi.org/10.1007/s10875-012-9768-y

61. Borghi S, Bournazos S, Thulin NK, Li C, Gajewski A, Sherwood RW, Zhang S, Harris E, Jagannathan P, Wang LX, Ravetch JV, Wang TT. FcRn, but not FcgammaRs, drives maternal-fetal transplacental transport of human IgG antibodies. Proc Natl Acad Sci U S A. 2020;117(23):12943-51. doi: 10.1073/pnas.2004325117. PubMed PMID: 32461366; PMCID: PMC7293622.

DOI: https://doi.org/10.1073/pnas.2004325117

62. Firan M, Bawdon R, Radu C, Ober RJ, Eaken D, Antohe F, Ghetie V, Ward ES. The MHC class I-related receptor, FcRn, plays an essential role in the maternofetal transfer of gamma-globulin in humans. Int Immunol. 2001;13(8):993-1002. doi: 10.1093/intimm/13.8.993. PubMed PMID: 11470769.

DOI: https://doi.org/10.1093/intimm/13.8.993

63. Vaccaro C, Bawdon R, Wanjie S, Ober RJ, Ward ES. Divergent activities of an engineered antibody in murine and human systems have implications for therapeutic antibodies. Proc Natl Acad Sci U S A. 2006;103(49):18709-14. doi: 10.1073/pnas.0606304103. PubMed PMID: 17116867; PMCID: PMC1693727.

DOI: https://doi.org/10.1073/pnas.0606304103

64. Herbst R, Wang Y, Gallagher S, Mittereder N, Kuta E, Damschroder M, Woods R, Rowe DC, Cheng L, Cook K, Evans K, Sims GP, Pfarr DS, Bowen MA, Dall’Acqua W, Shlomchik M, Tedder TF, Kiener P, Jallal B, Wu H, Coyle AJ. B-cell depletion in vitro and in vivo with an afucosylated anti-CD19 antibody. J Pharmacol Exp Ther. 2010;335(1):213-22. doi: 10.1124/jpet.110.168062. PubMed PMID: 20605905.

DOI: https://doi.org/10.1124/jpet.110.168062

65. Mori K, Iida S, Yamane-Ohnuki N, Kanda Y, Kuni-Kamochi R, Nakano R, Imai-Nishiya H, Okazaki A, Shinkawa T, Natsume A, Niwa R, Shitara K, Satoh M. Non-fucosylated therapeutic antibodies: the next generation of therapeutic antibodies. Cytotechnology. 2007;55(2-3):109-14. doi: 10.1007/s10616-007-9103-2. PubMed PMID: 19003000; PMCID: PMC2104554.

DOI: https://doi.org/10.1007/s10616-007-9103-2

66. Notermans DW, de Jong JJ, Goudsmit J, Bakker M, Roos MT, Nijholt L, Cremers J, Hellings JA, Danner SA, de Ronde A. Potent antiretroviral therapy initiates normalization of hypergammaglobulinemia and a decline in HIV type 1-specific antibody responses. AIDS Res Hum Retroviruses. 2001;17(11):1003-8. doi: 10.1089/088922201300343681. PubMed PMID: 11485617.

DOI: https://doi.org/10.1089/088922201300343681

67. Tong X, McNamara RP, Avendano MJ, Serrano EF, Garcia-Salum T, Pardo-Roa C, Bertera HL, Chicz TM, Levican J, Poblete E, Salinas E, Munoz A, Riquelme A, Alter G, Medina RA. Waning and boosting of antibody Fc-effector functions upon SARS-CoV-2 vaccination. Nature communications. 2023;14(1):4174. doi: 10.1038/s41467-023-39189-8. PubMed PMID: 37443074; PMCID: PMC10345146.

DOI: https://doi.org/10.1038/s41467-023-39189-8

68. Mahan AE, Jennewein MF, Suscovich T, Dionne K, Tedesco J, Chung AW, Streeck H, Pau M, Schuitemaker H, Francis D, Fast P, Laufer D, Walker BD, Baden L, Barouch DH, Alter G. Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination. PLoS Pathog. 2016;12(3):e1005456. doi: 10.1371/journal.ppat.1005456. PubMed PMID: 26982805; PMCID: PMC4794126.

DOI: https://doi.org/10.1371/journal.ppat.1005456

69. Jennewein MF, Alter G. The Immunoregulatory Roles of Antibody Glycosylation. Trends in immunology. 2017;38(5):358-72. doi: 10.1016/j.it.2017.02.004. PubMed PMID: 28385520.

DOI: https://doi.org/10.1016/j.it.2017.02.004

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