IgM- and IgA-response of peritoneal B-1 cells to the TI-2 antigen with the presence of γδT cells in vitro
https://doi.org/10.15789/1563-0625-IAI-2157
Abstract
IgA is an important component of the mucosal system of the body. It limits penetration of pathogens into the bloodstream. Inflammatory diseases such as Crohn disease and colitis may be associated with disorders of IgA synthesis. Both B1 and B2 cells are a source of IgA in the intestines. Special attention is paid to B1 cells, which are able to respond to T-independent type 2 antigens and produce natural antibodies. B1 cells produce about 50% of the intestinal IgA including specific antibodies to the components of microorganisms contained in the gastrointestinal tract. The mechanism of IgA formation in the T-independent way is not investigated in details. It was suggested that the γδТ-cells promote switching to IgA synthesis by B1 cells. This assumption may be supported by their co-localization with B1 lymphocytes in the intestinal mucosa, as well as participation, along with B1 cells, in formation of the first-line defense against the pathogens. In addition, the both lymphocyte subpopulations evolve during initial ontogenesis, earlier than “classic” В2 and αβT cells. Therefore, it was suggested that γδT lymphocytes may be involved into the processes of induction and/or regulation of IgM and IgA production by B1 cells in response to TH2 antigens.
In the present study, we have shown the effect of γδT cells upon generation of IgM- and IgA-forming B1 cells in response to α-1,3-dextran in vitro. We also studied the dynamics of the mRNA expression for IgM- and IgA-heavy chains by the B1 cells at different terms of in vitro culture.
It was found that, during co-cultivation of B1 cells with 20% γδT lymphocytes, there is no increase in the number of dextran-specific IgM-producing cells. The B1 cells exhibited an increase of IgM heavy chain mRNA expression in response to dextran but not in co-cultures. Expression of mRNA for IgM heavy chains in co-cultures was decreased compared to non-treated B-cell cultures. Contrary to the earlier assumption, a presence of γδT lymphocytes in culture did not enhance the formation of IgA producents. The obtained data suggest regulatory properties of the γδТ lymphocytes during the B1 cells response to T-independent antigens.
About the Authors
N. A. SnegirevaRussian Federation
Research Associate, Immunoglobulin Biosynthesis Laboratory,
Moscow
E. V. Sidorova
Russian Federation
PhD, MD (Biology), Professor, Head, Immunoglobulin Biosynthesis Laboratory,
Moscow
I. N. Dyakov
Russian Federation
PhD (Biology), Head, Immunoglobulin Biosynthesis Laboratory,
Moscow
M. V. Gavrilova
Russian Federation
PhD (Biology), Research Associate, Immunoglobulin Biosyntesis Laboratory,
Moscow
I. N. Chernyshova
Russian Federation
PhD (Medicine), Senior Research Associate, Immunoglobulin Biosyntesis Laboratory,
Moscow
E. P. Pashkov
Russian Federation
PhD, MD (Medicine), Professor, Department of Microbiology, Virology and Immunology,
Moscow
O. A. Svitich
Russian Federation
PhD, MD (Medicine), Corresponding Member, Russian Academy of Sciences, Director;
Professor, Department of Microbiology, Virology and Immunology,
Moscow
References
1. Gavrilova M.V., Snegireva N.A., Sidorova E.V. Influence of Breg and IL-10 upon humoral immune response. Meditsinskaya immunologiya = Medical Immunology (Russia), 2016, Vol. 18, no. 4, pp. 331-338. (In Russ.) doi: 10.15789/1563-0625-2016-4-331-338.
2. Gavrilova M.V., Chernyshova I.N., Khochenkov D.A., Sidorova E.V. In vitro cellular interactions during immune response to t cellindependent type 2 antigens. Meditsinskaya immunologiya = Medical Immunology (Russia), 2013, Vol. 15, no. 4, pp. 325-334. (In Russ.) doi: 10.15789/1563-0625-2013-4-325-334.
3. Dyakov I.N., Gavrilova M.V., Chernyshova I.N., Sidorova E.V. The influence of microenvironment on the functional activity of murine B lymphocytes. Biologicheskie membrany: Zhurnal membrannoy i kletochnoy biologii = Biochemistry (Moscow) Supplement. Series A: Membrane And Cell Biology, 2008, Vol. 25, no. 5, pp. 360-366. (In Russ.)
4. Dyakov I.N., Grigoriev I.V., Sidorova E.V., Chernyshova I.N. Functional activity of murine b cell: a role of microenvironment. Meditsinskaya immunologiya = Medical Immunology (Russia), 2008, Vol. 10, no. 1, pp. 51-58. (In Russ.) doi: 10.15789/1563-0625-2008-1-51-58.
5. Karkischenko N.N. Biomedicine alternatives. Part 2. Classical and Alternative Pharmacotoxicology. Moscow: VPK, 2007. 448 p.
6. Molecular and cellular basis of immune regulation, immune and immunodiagnostics (experimental models). Meditsinskaya immunologiya = Medical Immunology (Russia), 2015, Vol. 17, no. 3s, pp. 9-56. (In Russ.) doi.:10.15789/1563-0625- 2015-3s-9-56.
7. Nizhegorodova D.B., Zafranskaya M.M. γδТ-lymphocytes: general characteristics, subpopulation profile, biological role, and functional features. Meditsinskaya immunologiya = Medical Immunology (Russia), 2009, Vol. 11, no. 2-3, pp. 115-130. (In Russ.) doi: 10.15789/1563-0625-2009-2-3-115-130.
8. Chernyshova I.N., Gavrilova M.V., Sidorova E.V. Model system to study cell interactions and mechanisms of immune response to T-independent type 2 antigens in vitro. Biologicheskie membrany: zhurnal membrannoy i kletochnoy biologii = Biochemistry (Moscow) Supplement. Series A: Membrane and Cell Biology, 2010, Vol. 27, no. 5, pp. 1-7. (In Russ.)
9. Allaire J.M., Crowley S.M., Law H.T., Chang S.Y., Ko H.J., Vallance B.A. The intestinal epithelium: central coordinator of mucosal immunity. Trends Immunol., 2018, Vol. 39, no. 9, pp. 677-696.
10. Aziz M., Holodick N.E., Rothstein T.L., Wang P. The role of B-1 cells in inflammation. Immunol. Res., 2015, Vol. 63, no. 1-3, pp. 153-166.
11. Baumgarth N. The double life of a B-1 cell: self-reactivity selects for protective effector functions. Nat. Rev. Immunol., 2011, Vol. 11, no. 1, pp. 34-46.
12. Born W.K., Huang Y., Reinhardt R.L., Huang H., Sun D., O’Brien R.L. γδ T Cells and B Cells. Adv. Immunol., 2017, Vol. 134, pp. 1-45.
13. Born W., Cady C., Jones-Carson J., Mukasa A., Lahn M., O’Brien R. Immunoregulatory functions of gammadelta T cells. Adv. Immunol., 1999, Vol. 71, pp. 77-144.
14. Chien Y.H., Meyer C., Bonneville M. γδ T cells: first line of defense and beyond. Annu. Rev. Immunol., 2014, Vol. 32, pp. 121-155.
15. Fagarasan S., Honjo T. Regulation of IgA synthesis at mucosal surfaces. Curr. Opin. Immunol., 2004, Vol. 16, no. 3, pp. 277-283.
16. Fagarasan S., Honjo T. T-Independent immune response: new aspects of B cell biology. Science, 2000, Vol. 290, no. 5489, pp. 89-92.
17. Fagarasan S., Kawamoto S., Kanagawa O., Suzuki K. Adaptive immune regulation in the gut: T celldependent and T cell-independent IgA synthesis. Annu. Rev. Immunol., 2010, Vol. 28, pp. 243-273.
18. Fagarasan S., Kinoshita K., Muramatsu M., Ikuta K., Honjo T. In situ class switching and differentiation to IgA-producing cells in the gut lamina propria. Nature, 2001, Vol. 413, no. 6856, pp. 639-643.
19. Fay N.S., Larson E.C., Jameson J.M. Chronic inflammation and γδ T Cells. Front. Immunol., 2016, Vol. 7, 210. doi: 10.3389/fimmu.2016.00210.
20. Fujihashi K., McGhee J.R., Kweon M.N., Cooper M.D., Tonegawa S., Takahashi I., Hiroi T., Mestecky J., Kiyono H. gamma/delta T cell-deficient mice have impaired mucosal immunoglobulin A responses. J. Exp. Med., 1996, Vol. 183, no. 4, pp. 1929-1935.
21. Gärdby E., Wrammert J., Schön K., Ekman L., Leanderson T., Lycke N. Strong differential regulation of serum and mucosal IgA responses as revealed in CD28-deficient mice using cholera toxin adjuvant. J. Immunol., 2003, Vol. 170, no. 1, pp. 55-63.
22. Genestier L., Taillardet M., Mondiere P., Gheit H., Bella C., Defrance T. TLR agonists selectively promote terminal plasma cell differentiation of B cell subsets specialized in thymus-independent responses. J. Immunol., 2007, Vol. 178, no. 12, pp. 7779-7786.
23. Huang, Y., Getahun, A., Heiser, R.A., Detanico, T., Aviszus, K., Kirchenbaum, G. et al. Gammadelta T cells shape preimmune peripheral B cell populations. J. Immunol., 2016, Vol. 196, pp. 217-231.
24. Kober O.I., Ahl D., Pin C., Holm L., Carding S.R., Juge N. γδ T-cell-deficient mice show alterations in mucin expression, glycosylation, and goblet cells but maintain an intact mucus layer. Am. J. Physiol. Gastrointest. Liver Physiol., 2014, Vol. 306, no. 7, pp. G582-G593.
25. Macpherson A.J., Gatto D., Sainsbury E., Harriman G.R., Hengartner H., Zinkernagel R.M. A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science, 2000, Vol. 288, no. 5474, pp. 2222-2226.
26. Mann E.R., McCarthy N.E., Peake S.T., Milestone A.N., Al-Hassi H.O., Bernardo D., Tee C.T., Landy J., Pitcher M.C., Cochrane S.A., Hart A.L., Stagg A.J., Knight S.C. Skin- and gut-homing molecules on human circulating γδ T cells and their dysregulation in inflammatory bowel disease. Clin. Exp. Immunol., 2012, Vol. 170, no. 2, pp. 122-130.
27. Meyer-Bahlburg A. B-1 cells as a source of IgA. Ann. N.-Y. Acad. Sci., 2015, Vol. 1362, pp. 122-131.
28. Mond J.J., Vos Q., Lees A., Snapper C.M. T cell independent antigens. Curr. Opin. Immunol., 1995, Vol. 7, no. 3, pp. 349-354.
29. Nielsen M.M., Witherden D.A., Havran W.L. γδ T cells in homeostasis and host defence of epithelial barrier tissues. Nat. Rev. Immunol., 201, Vol. 17, no. 12, pp. 733-745.
30. Pabst O. New concepts in the generation and functions of IgA. Nat. Rev. Immunol., 2012, Vol. 12, no. 12, pp. 821-832.
31. Paul S., Lal G. Regulatory and effector functions of gamma-delta (γδ) T cells and their therapeutic potential in adoptive cellular therapy for cancer. Int. J. Cancer, 2016, Vol. 139, no. 5, pp. 976-985.
32. Rezende R.M., Lanser A.J., Rubino S., Kuhn C., Skillin N., Moreira T.G., Liu S., Gabriely G., David B.A., Menezes G.B., Weiner H.L. γδ T cells control humoral immune response by inducing T follicular helper cell differentiation. Nat. Commun., 2018, Vol. 9, no. 1, 3151. doi: 10.1038/s41467-018-05487-9.
33. Rothstein T.L., Griffin D.O., Holodick N.E., Quach T.D., Kaku H. Human B-1 cells take the stage. Ann. N.-Y. Acad. Sci., 2013, Vol. 1285, pp. 97-114.
34. Roy B., Agarwal S., Brennecke A., Krey M., Pabst O., Düber S., Weiss S. B-1-cell subpopulations contribute differently to gut immunity. Eur. J. Immunol., 2013, Vol. 43, pp. 2023-2032.
35. Shao W., Zhang C., Liu E., Zhang L., Ma J., Zhu Z., Gong X., Qin Z., Qiu X. Identification of liver epithelial cell-derived Ig expression in μ chain-deficient mice. Sci. Rep., 2016, Vol. 6, 23669. Available at: https://www.nature.com/articles/srep23669.
36. Shimomura Y., Mizoguchi E., Sugimoto K., Kibe R., Benno Y., Mizoguchi A., Bhan A.K. Regulatory role of B-1 B cells in chronic colitis. Int. Immunol., 2008, Vol. 20, no. 6, pp. 729-737.
37. Singh K., Chang C., Gershwin M.E. IgA deficiency and autoimmunity. Autoimmun. Rev., 2014, Vol. 13, pp. 163-177.
38. Snegireva N., Gavrilova M., Sidorova E. Isolation of γδT cells from mouse small intestine. Open J. Immunol., 2013, Vol. 3, No.4, 221-223.
39. Tougaard P., Skov S., Pedersen A.E., Krych L., Nielsen D.S., Bahl M.I., Christensen E.G., Licht T.R., Poulsen S.S., Metzdorff S.B., Hansen A.K., Hansen C.H. TL1A regulates TCRγδ+ intraepithelial lymphocytes and gut microbial composition. Eur. J. Immunol., 2015, Vol. 45, no. 3, pp. 865-875.
40. van Praet J.T., Donovan E., Vanassche I., Drennan M.B., Windels F., Dendooven A., Allais L., Cuvelier C.A., van de Loo F., Norris P.S., Kruglov A.A., Nedospasov S.A., Rabot S., Tito R., Raes J., Gaboriau-Routhiau V., Cerf-Bensussan N., van de Wiele T., Eberl G., Ware C.F., Elewaut D. Commensal microbiota influence systemic autoimmune responses. EMBO J., 2015, Vol. 34, no. 4, pp. 466-474.
41. Watanabe N., Ikuta K., Fagarasan S., Yazumi S., Chiba T., Honjo T. Migration and differentiation of autoreactive B-1 cells induced by activated gamma/delta T cells in antierythrocyte immunoglobulin transgenic mice. J. Exp. Med., 2000, Vol. 192, no. 11, pp. 1577-1586.
Supplementary files
Review
For citations:
Snegireva N.A., Sidorova E.V., Dyakov I.N., Gavrilova M.V., Chernyshova I.N., Pashkov E.P., Svitich O.A. IgM- and IgA-response of peritoneal B-1 cells to the TI-2 antigen with the presence of γδT cells in vitro. Medical Immunology (Russia). 2021;23(2):245-256. (In Russ.) https://doi.org/10.15789/1563-0625-IAI-2157