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The function of γδ T cells in humoral immune responses

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  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this review is to discuss the role of γδ T cells played in humoral immune responses.

Background

The γδ T cell receptor (γδ TCR) recognizes antigens, including haptens and proteins, in an MHC-independent manner. The recognition of these antigens by γδ TCRs crosses antigen recognition by the B cell receptors (BCRs), suggesting that γδ T cells may be involved in the process of antigen recognition and activation of B cells. However, the role of γδ T cells in humoral immune responses is still less clear.

Methods

The kinds of literature about the γδ T cell-B cell interaction were searched on PubMed with search terms, such as γδ T cells, antibody, B cell responses, antigen recognition, and infection.

Results

Accumulating evidence indicates that γδ T cells, independent of αβ T cells, participate in multiple steps of humoral immunity, including B cell maturation, activation and differentiation, antibody production and class switching. Mechanically, γδ T cells affect B cell function by directly interacting with B cells, secreting cytokines, or modulating αβ T cells.

Conclusion

In this review, we summarize current knowledge on how γδ T cells take part in the humoral immune response, which may assist future vaccine design.

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Data availability

The datasets generated during this review are available from the corresponding author upon reasonable request.

References

  1. Craig NL. V(D)J recombination and transposition: closer than expected. Science. 1996;271:1512. https://doi.org/10.1126/science.271.5255.1512.

    Article  CAS  PubMed  Google Scholar 

  2. Papavasiliou F, Casellas R, Suh H, Qin XF, Besmer E, Pelanda R, Nemazee D, Rajewsky K, Nussenzweig MC. V(D)J recombination in mature B cells: a mechanism for altering antibody responses. Science. 1997;278:298–301. https://doi.org/10.1126/science.278.5336.298.

    Article  CAS  PubMed  Google Scholar 

  3. Rock EP, Sibbald PR, Davis MM, Chien YH. CDR3 length in antigen-specific immune receptors. J Exp Med. 1994;179:323–8. https://doi.org/10.1084/jem.179.1.323.

    Article  CAS  PubMed  Google Scholar 

  4. Chien YH, Konigshofer Y. Antigen recognition by gammadelta T cells. Immunol Rev. 2007;215:46–58. https://doi.org/10.1111/j.1600-065X.2006.00470.x.

    Article  CAS  PubMed  Google Scholar 

  5. Shin S, El-Diwany R, Schaffert S, Adams EJ, Garcia KC, Pereira P, Chien YH. Antigen recognition determinants of gammadelta T cell receptors. Science. 2005;308:252–5. https://doi.org/10.1126/science.1106480.

    Article  CAS  PubMed  Google Scholar 

  6. Selin LK, Santolucito PA, Pinto AK, Szomolanyi-Tsuda E, Welsh RM. Innate immunity to viruses: control of vaccinia virus infection by gamma delta T cells. J Immunol. 2001;166:6784–94. https://doi.org/10.4049/jimmunol.166.11.6784.

    Article  CAS  PubMed  Google Scholar 

  7. Wang T, Gao Y, Scully E, Davis CT, Anderson JF, Welte T, Ledizet M, Koski R, Madri JA, Barrett A, et al. Gamma delta T cells facilitate adaptive immunity against West Nile virus infection in mice. J Immunol. 2006;177:1825–32. https://doi.org/10.4049/jimmunol.177.3.1825.

    Article  CAS  PubMed  Google Scholar 

  8. Zeng X, Wei YL, Huang J, Newell EW, Yu H, Kidd BA, Kuhns MS, Waters RW, Davis MM, Weaver CT, et al. gammadelta T cells recognize a microbial encoded B cell antigen to initiate a rapid antigen-specific interleukin-17 response. Immunity. 2012;37:524–34. https://doi.org/10.1016/j.immuni.2012.06.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Zeng X, Meyer C, Huang J, Newell EW, Kidd BA, Wei YL, Chien YH. Gamma delta T cells recognize haptens and mount a hapten-specific response. Elife. 2014;3:e03609. https://doi.org/10.7554/eLife.03609.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Eberl M. Antigen recognition by human γδ T cells: one step closer to knowing. Immunol Cell Biol. 2020;98:351–4. https://doi.org/10.1111/imcb.12334.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Hayday AC. γδ T cell update: adaptate orchestrators of immune surveillance. J Immunol. 2019;203:311–20. https://doi.org/10.4049/jimmunol.1800934.

    Article  CAS  PubMed  Google Scholar 

  12. Castillo-González R, Cibrian D, Sánchez-Madrid F. Dissecting the complexity of γδ T-cell subsets in skin homeostasis, inflammation, and malignancy. J Allergy Clin Immunol. 2021;147:2030–42. https://doi.org/10.1016/j.jaci.2020.11.023.

    Article  CAS  PubMed  Google Scholar 

  13. Cai Y, Shen X, Ding C, Qi C, Li K, Li X, Jala VR, Zhang HG, Wang T, Zheng J, et al. Pivotal role of dermal IL-17-producing γδ T cells in skin inflammation. Immunity. 2011;35:596–610. https://doi.org/10.1016/j.immuni.2011.08.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Carding SR, Egan PJ. Gammadelta T cells: functional plasticity and heterogeneity. Nat Rev Immunol. 2002;2:336–45. https://doi.org/10.1038/nri797.

    Article  CAS  PubMed  Google Scholar 

  15. Simonian PL, Roark CL, Wehrmann F, Lanham AM, Born WK, O’Brien RL, Fontenot AP. IL-17A-expressing T cells are essential for bacterial clearance in a murine model of hypersensitivity pneumonitis. J Immunol. 2009;182:6540–9. https://doi.org/10.4049/jimmunol.0900013.

    Article  CAS  PubMed  Google Scholar 

  16. Hoytema van Konijnenburg DP, Reis BS, Pedicord VA, Farache J, Victora GD, Mucida D. Intestinal epithelial and intraepithelial T cell crosstalk mediates a dynamic response to infection. Cell. 2017;171:783-794.e713. https://doi.org/10.1016/j.cell.2017.08.046.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kaminski H, Marsères G, Cosentino A, Guerville F, Pitard V, Fournié JJ, Merville P, Déchanet-Merville J, Couzi L. Understanding human γδ T cell biology toward a better management of cytomegalovirus infection. Immunol Rev. 2020;298:264–88. https://doi.org/10.1111/imr.12922.

    Article  CAS  PubMed  Google Scholar 

  18. Willcox BE, Willcox CR. γδ TCR ligands: the quest to solve a 500-million-year-old mystery. Nat Immunol. 2019;20:121–8. https://doi.org/10.1038/s41590-018-0304-y.

    Article  CAS  PubMed  Google Scholar 

  19. Melandri D, Zlatareva I, Chaleil RAG, Dart RJ, Chancellor A, Nussbaumer O, Polyakova O, Roberts NA, Wesch D, Kabelitz D, et al. The γδTCR combines innate immunity with adaptive immunity by utilizing spatially distinct regions for agonist selection and antigen responsiveness. Nat Immunol. 2018;19:1352–65. https://doi.org/10.1038/s41590-018-0253-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Crowley MP, Fahrer AM, Baumgarth N, Hampl J, Gutgemann I, Teyton L, Chien Y. A population of murine gammadelta T cells that recognize an inducible MHC class Ib molecule. Science. 2000;287:314–6. https://doi.org/10.1126/science.287.5451.314.

    Article  CAS  PubMed  Google Scholar 

  21. Wang X, Lin X, Zheng Z, Lu B, Wang J, Tan AH, Zhao M, Loh JT, Ng SW, Chen Q, et al. Host-derived lipids orchestrate pulmonary γδ T cell response to provide early protection against influenza virus infection. Nat Commun. 2021;12:1914. https://doi.org/10.1038/s41467-021-22242-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bansal RR, Mackay CR, Moser B, Eberl M. IL-21 enhances the potential of human γδ T cells to provide B-cell help. Eur J Immunol. 2012;42:110–9. https://doi.org/10.1002/eji.201142017.

    Article  CAS  PubMed  Google Scholar 

  23. Mathew NR, Jayanthan JK, Smirnov IV, Robinson JL, Axelsson H, Nakka SS, Emmanouilidi A, Czarnewski P, Yewdell WT, Schön K, et al. Single-cell BCR and transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific B cells. Cell Rep. 2021;35:109286. https://doi.org/10.1016/j.celrep.2021.109286.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Qin XF, Reichlin A, Luo Y, Roeder RG, Nussenzweig MC. OCA-B integrates B cell antigen receptor-, CD40L- and IL 4-mediated signals for the germinal center pathway of B cell development. Embo J. 1998;17:5066–75. https://doi.org/10.1093/emboj/17.17.5066.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Yewdell WT, Smolkin RM, Belcheva KT, Mendoza A, Michaels AJ, Cols M, Angeletti D, Yewdell JW, Chaudhuri J. Temporal dynamics of persistent germinal centers and memory B cell differentiation following respiratory virus infection. Cell Rep. 2021;37:109961. https://doi.org/10.1016/j.celrep.2021.109961.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sperling AI, Wortis HH. CD4-, CD8- gamma/delta cells from normal mice respond to a syngeneic B cell lymphoma and can induce its differentiation. Int Immunol. 1989;1:434–42. https://doi.org/10.1093/intimm/1.4.434.

    Article  CAS  PubMed  Google Scholar 

  27. Vidovic D, Dembic Z. Qa-1 restricted gamma delta T cells can help B cells. Curr Top Microbiol Immunol. 1991;173:239–44.

    CAS  PubMed  Google Scholar 

  28. Zheng B, Marinova E, Han J, Tan TH, Han S. Cutting edge: gamma delta T cells provide help to B cells with altered clonotypes and are capable of inducing Ig gene hypermutation. J Immunol. 2003;171:4979–83. https://doi.org/10.4049/jimmunol.171.10.4979.

    Article  CAS  PubMed  Google Scholar 

  29. Su D, Shen M, Li X, Sun L. Roles of γδ T cells in the pathogenesis of autoimmune diseases. Clin Dev Immunol. 2013;2013:985753. https://doi.org/10.1155/2013/985753.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Pao W, Wen L, Smith AL, Gulbranson-Judge A, Zheng B, Kelsoe G, MacLennan IC, Owen MJ, Hayday AC. Gamma delta T cell help of B cells is induced by repeated parasitic infection, in the absence of other T cells. Curr Biol. 1996;6:1317–25. https://doi.org/10.1016/s0960-9822(02)70718-5.

    Article  CAS  PubMed  Google Scholar 

  31. Huang Y, Getahun A, Heiser RA, Detanico TO, Aviszus K, Kirchenbaum GA, Casper TL, Huang C, Aydintug MK, Carding SR, et al. γδ T cells shape preimmune peripheral B cell populations. J Immunol. 2016;196:217–31. https://doi.org/10.4049/jimmunol.1501064.

    Article  CAS  PubMed  Google Scholar 

  32. Weinstein JA, Zeng X, Chien YH, Quake SR. Correlation of gene expression and genome mutation in single B-cells. PLoS ONE. 2013;8:e67624. https://doi.org/10.1371/journal.pone.0067624.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Karunakaran MM, Willcox CR, Salim M, Paletta D, Fichtner AS, Noll A, Starick L, Nöhren A, Begley CR, Berwick KA, et al. Butyrophilin-2A1 directly binds germline-encoded regions of the Vγ9Vδ2 TCR and is essential for phosphoantigen sensing. Immunity. 2020;52:487-498.e486. https://doi.org/10.1016/j.immuni.2020.02.014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rigau M, Ostrouska S, Fulford TS, Johnson DN, Woods K, Ruan Z, McWilliam HEG, Hudson C, Tutuka C, Wheatley AK, et al. Butyrophilin 2A1 is essential for phosphoantigen reactivity by γδ T cells. Science. 2020. https://doi.org/10.1126/science.aay5516.

    Article  PubMed  Google Scholar 

  35. Blazquez JL, Benyamine A, Pasero C, Olive D. New insights into the regulation of γδ T cells by BTN3A and other BTN/BTNL in tumor immunity. Front Immunol. 2018;9:1601. https://doi.org/10.3389/fimmu.2018.01601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Russano AM, Agea E, Corazzi L, Postle AD, De Libero G, Porcelli S, de Benedictis FM, Spinozzi F. Recognition of pollen-derived phosphatidyl-ethanolamine by human CD1d-restricted gamma delta T cells. J Allergy Clin Immunol. 2006;117:1178–84. https://doi.org/10.1016/j.jaci.2006.01.001.

    Article  CAS  PubMed  Google Scholar 

  37. Delia D, Cattoretti G, Polli N, Fontanella E, Aiello A, Giardini R, Rilke F, Della Porta G. CD1c but neither CD1a nor CD1b molecules are expressed on normal, activated, and malignant human B cells: identification of a new B-cell subset. Blood. 1988;72:241–7.

    Article  CAS  PubMed  Google Scholar 

  38. Zheng Z, Venkatapathy S, Rao G, Harrington CA. Expression profiling of B cell chronic lymphocytic leukemia suggests deficient CD1-mediated immunity, polarized cytokine response, altered adhesion and increased intracellular protein transport and processing of leukemic cells. Leukemia. 2002;16:2429–37. https://doi.org/10.1038/sj.leu.2402711.

    Article  CAS  PubMed  Google Scholar 

  39. Brandes M, Willimann K, Lang AB, Nam KH, Jin C, Brenner MB, Morita CT, Moser B. Flexible migration program regulates gamma delta T-cell involvement in humoral immunity. Blood. 2003;102:3693–701. https://doi.org/10.1182/blood-2003-04-1016.

    Article  CAS  PubMed  Google Scholar 

  40. Petrasca A, Melo AM, Breen EP, Doherty DG. Human Vδ3(+) γδ T cells induce maturation and IgM secretion by B cells. Immunol Lett. 2018;196:126–34. https://doi.org/10.1016/j.imlet.2018.02.002.

    Article  CAS  PubMed  Google Scholar 

  41. Caccamo N, Battistini L, Bonneville M, Poccia F, Fournié JJ, Meraviglia S, Borsellino G, Kroczek RA, La Mendola C, Scotet E, et al. CXCR5 identifies a subset of Vgamma9Vdelta2 T cells which secrete IL-4 and IL-10 and help B cells for antibody production. J Immunol. 2006;177:5290–5. https://doi.org/10.4049/jimmunol.177.8.5290.

    Article  CAS  PubMed  Google Scholar 

  42. Raju S, Kretzmer LZ, Koues OI, Payton JE, Oltz EM, Cashen A, Polic B, Schreiber RD, Shaw AS, Markiewicz MA. NKG2D-NKG2D ligand interaction inhibits the outgrowth of naturally arising low-grade B cell lymphoma in vivo. J Immunol. 2016;196:4805–13. https://doi.org/10.4049/jimmunol.1501982.

    Article  CAS  PubMed  Google Scholar 

  43. Nückel H, Switala M, Sellmann L, Horn PA, Dürig J, Dührsen U, Küppers R, Grosse-Wilde H, Rebmann V. The prognostic significance of soluble NKG2D ligands in B-cell chronic lymphocytic leukemia. Leukemia. 2010;24:1152–9. https://doi.org/10.1038/leu.2010.74.

    Article  CAS  PubMed  Google Scholar 

  44. Pistoia V, Tumino N, Vacca P, Veneziani I, Moretta A, Locatelli F, Moretta L. Human γδ T-cells: from surface receptors to the therapy of high-risk leukemias. Front Immunol. 2018;9:984. https://doi.org/10.3389/fimmu.2018.00984.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Dai YM, Liu HY, Liu YF, Zhang Y, He W. EBV transformation induces overexpression of hMSH2/3/6 on B lymphocytes and enhances γδT-cell-mediated cytotoxicity via TCR and NKG2D. Immunology. 2018;154:673–82. https://doi.org/10.1111/imm.12920.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Jamieson AM, Diefenbach A, McMahon CW, Xiong N, Carlyle JR, Raulet DH. The role of the NKG2D immunoreceptor in immune cell activation and natural killing. Immunity. 2002;17:19–29. https://doi.org/10.1016/s1074-7613(02)00333-3.

    Article  CAS  PubMed  Google Scholar 

  47. Moser B, Eberl M. γδ T-APCs: a novel tool for immunotherapy? Cell Mol Life Sci. 2011;68:2443–52. https://doi.org/10.1007/s00018-011-0706-6.

    Article  CAS  PubMed  Google Scholar 

  48. Rezende RM, Lanser AJ, Rubino S, Kuhn C, Skillin N, Moreira TG, Liu S, Gabriely G, David BA, Menezes GB, et al. γδ T cells control humoral immune response by inducing T follicular helper cell differentiation. Nat Commun. 2018;9:3151. https://doi.org/10.1038/s41467-018-05487-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Koutsakos M, Wheatley AK, Loh L, Clemens EB, Sant S, Nüssing S, Fox A, Chung AW, Laurie KL, Hurt AC, et al. Circulating T(FH) cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity. Sci Transl Med. 2018. https://doi.org/10.1126/scitranslmed.aan8405.

    Article  PubMed  Google Scholar 

  50. Han HJ, Jang YS, Seo GY, Park SG, Kang SG, Yoon SI, Ko HJ, Lee GS, Kim PH. Murine γδ T cells render B cells refractory to commitment of IgA isotype switching. Immune Netw. 2018;18:e25. https://doi.org/10.4110/in.2018.18.e25.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Park K-H, Seo G-Y, Jang Y-S, Kim P-H. TGF-β and BAFF derived from CD4+CD25+Foxp3+ T cells mediate mouse IgA isotype switching. Genes Genom. 2012;34:619–25. https://doi.org/10.1007/s13258-012-0062-4.

    Article  CAS  Google Scholar 

  52. Huang Y, Jin N, Roark CL, Aydintug MK, Wands JM, Huang H, O’Brien RL, Born WK. The influence of IgE-enhancing and IgE-suppressive gammadelta T cells changes with exposure to inhaled ovalbumin. J Immunol. 2009;183:849–55. https://doi.org/10.4049/jimmunol.0804104.

    Article  CAS  PubMed  Google Scholar 

  53. Cook L, Miyahara N, Jin N, Wands JM, Taube C, Roark CL, Potter TA, Gelfand EW, O’Brien RL, Born WK. Evidence that CD8+ dendritic cells enable the development of gammadelta T cells that modulate airway hyperresponsiveness. J Immunol. 2008;181:309–19. https://doi.org/10.4049/jimmunol.181.1.309.

    Article  CAS  PubMed  Google Scholar 

  54. Huang Y, Heiser RA, Detanico TO, Getahun A, Kirchenbaum GA, Casper TL, Aydintug MK, Carding SR, Ikuta K, Huang H, et al. γδ T cells affect IL-4 production and B-cell tolerance. Proc Natl Acad Sci USA. 2015;112:E39-48. https://doi.org/10.1073/pnas.1415107111.

    Article  CAS  PubMed  Google Scholar 

  55. Hidaka T, Kitani A, Hara M, Harigai M, Suzuki K, Kawaguchi Y, Ishizuka T, Kawagoe M, Nakamura H. IL-4 down-regulates the surface expression of CD5 on B cells and inhibits spontaneous immunoglobulin and IgM-rheumatoid factor production in patients with rheumatoid arthritis. Clin Exp Immunol. 1992;89:223–9. https://doi.org/10.1111/j.1365-2249.1992.tb06936.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Inoue SI, Niikura M, Asahi H, Kawakami Y, Kobayashi F. γδ T cells modulate humoral immunity against Plasmodium berghei infection. Immunology. 2018;155:519–32. https://doi.org/10.1111/imm.12997.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Pan T, Tan R, Li M, Liu Z, Wang X, Tian L, Liu J, Qu H. IL17-producing γδ T cells may enhance humoral immunity during pulmonary Pseudomonas aeruginosa infection in mice. Front Cell Infect Microbiol. 2016;6:170. https://doi.org/10.3389/fcimb.2016.00170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Duan L, Liu D, Chen H, Mintz MA, Chou MY, Kotov DI, Xu Y, An J, Laidlaw BJ, Cyster JG. Follicular dendritic cells restrict interleukin-4 availability in germinal centers and foster memory B cell generation. Immunity. 2021;54:2256-2272.e2256. https://doi.org/10.1016/j.immuni.2021.08.028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Finkelman FD, Katona IM, Mosmann TR, Coffman RL. IFN-gamma regulates the isotypes of Ig secreted during in vivo humoral immune responses. J Immunol. 1988;140:1022–7.

    Article  CAS  PubMed  Google Scholar 

  60. Stone SL, Peel JN, Scharer CD, Risley CA, Chisolm DA, Schultz MD, Yu B, Ballesteros-Tato A, Wojciechowski W, Mousseau B, et al. T-bet transcription factor promotes antibody-secreting cell differentiation by limiting the inflammatory effects of IFN-γ on B cells. Immunity. 2019;50:1172-1187.e1177. https://doi.org/10.1016/j.immuni.2019.04.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Cha H, Xie H, Jin C, Feng Y, Xie S, Xie A, Yang Q, Qi Y, Qiu H, Wu Q, et al. Adjustments of γδ T cells in the lung of Schistosoma japonicum-Infected C56BL/6 Mice. Front Immunol. 2020;11:1045. https://doi.org/10.3389/fimmu.2020.01045.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Huber S, Sartini D. T cells expressing the Vgamma1 T-cell receptor enhance virus-neutralizing antibody response during coxsackievirus B3 infection of BALB/c mice: differences in male and female mice. Viral Immunol. 2005;18:730–9. https://doi.org/10.1089/vim.2005.18.730.

    Article  CAS  PubMed  Google Scholar 

  63. Ullrich L, Lueder Y, Juergens AL, Wilharm A, Barros-Martins J, Bubke A, Demera A, Ikuta K, Patzer GE, Janssen A, et al. IL-4-producing Vγ1(+)/Vδ6(+) γδ T cells sustain germinal center reactions in Peyer’s patches of mice. Front Immunol. 2021;12:729607. https://doi.org/10.3389/fimmu.2021.729607.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Chu VT, Beller A, Rausch S, Strandmark J, Zänker M, Arbach O, Kruglov A, Berek C. Eosinophils promote generation and maintenance of immunoglobulin-A-expressing plasma cells and contribute to gut immune homeostasis. Immunity. 2014;40:582–93. https://doi.org/10.1016/j.immuni.2014.02.014.

    Article  CAS  PubMed  Google Scholar 

  65. Lindner C, Wahl B, Föhse L, Suerbaum S, Macpherson AJ, Prinz I, Pabst O. Age, microbiota, and T cells shape diverse individual IgA repertoires in the intestine. J Exp Med. 2012;209:365–77. https://doi.org/10.1084/jem.20111980.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Andreu-Ballester JC, Zamora V, Garcia-Ballesteros C, Benet-Campos C, Lopez-Chuliá F, Tormo-Calandín C, Cuéllar C. Anti-Anisakis sp. antibodies in serum of patients with sepsis and their relationship with γδ T cells and disease severity. Int J Parasitol. 2018;48:483–91. https://doi.org/10.1016/j.ijpara.2017.11.007.

    Article  CAS  PubMed  Google Scholar 

  67. Maloy KJ, Odermatt B, Hengartner H, Zinkernagel RM. Interferon gamma-producing gammadelta T cell-dependent antibody isotype switching in the absence of germinal center formation during virus infection. Proc Natl Acad Sci USA. 1998;95:1160–5. https://doi.org/10.1073/pnas.95.3.1160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Xie S, Li J, Wang JH, Wu Q, Yang P, Hsu HC, Smythies LE, Mountz JD. IL-17 activates the canonical NF-kappaB signaling pathway in autoimmune B cells of BXD2 mice to upregulate the expression of regulators of G-protein signaling 16. J Immunol. 2010;184:2289–96. https://doi.org/10.4049/jimmunol.0903133.

    Article  CAS  PubMed  Google Scholar 

  69. Subbarayal B, Chauhan SK, Di Zazzo A, Dana R. IL-17 augments b cell activation in ocular surface autoimmunity. J Immunol. 2016;197:3464–70. https://doi.org/10.4049/jimmunol.1502641.

    Article  CAS  PubMed  Google Scholar 

  70. Gertner-Dardenne J, Bonnafous C, Bezombes C, Capietto AH, Scaglione V, Ingoure S, Cendron D, Gross E, Lepage JF, Quillet-Mary A, et al. Bromohydrin pyrophosphate enhances antibody-dependent cell-mediated cytotoxicity induced by therapeutic antibodies. Blood. 2009;113:4875–84. https://doi.org/10.1182/blood-2008-08-172296.

    Article  CAS  PubMed  Google Scholar 

  71. Cheng ZF, Li HK, Yang HP, Lee CY, Tang SW, Lin YL, Hsiao SC. A novel endogenous CD16-expressing natural killer cell for cancer immunotherapy. Biochem Biophys Rep. 2021;26:100935. https://doi.org/10.1016/j.bbrep.2021.100935.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Junqueira C, Polidoro RB, Castro G, Absalon S, Liang Z, Sen Santara S, Crespo Â, Pereira DB, Gazzinelli RT, Dvorin JD, et al. γδ T cells suppress Plasmodium falciparum blood-stage infection by direct killing and phagocytosis. Nat Immunol. 2021;22:347–57. https://doi.org/10.1038/s41590-020-00847-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Couzi L, Pitard V, Sicard X, Garrigue I, Hawchar O, Merville P, Moreau JF, Déchanet-Merville J. Antibody-dependent anti-cytomegalovirus activity of human γδ T cells expressing CD16 (FcγRIIIa). Blood. 2012;119:1418–27. https://doi.org/10.1182/blood-2011-06-363655.

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the National Natural Science Foundation of China (32070899, 31870899) to X.Z.

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Authors and Affiliations

  1. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Lingfeng Qiu, Yixi Zhang & Xun Zeng

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  1. Lingfeng Qiu
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LQ, YZ, and XZ drafted the main body of this manuscript. XZ takes primary responsibility for this paper as the corresponding author. All authors contributed to the article and approved the submitted version.

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Correspondence to Xun Zeng.

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Qiu, L., Zhang, Y. & Zeng, X. The function of γδ T cells in humoral immune responses. Inflamm. Res. 72, 747–755 (2023). https://doi.org/10.1007/s00011-023-01704-4

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