DOI QR코드

DOI QR Code

Alum Directly Modulates Murine B Lymphocytes to Produce IgG1 Isotype

  • Jin, Bo-Ra (Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University) ;
  • Kim, Sun-Jin (Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University) ;
  • Lee, Jeong-Min (Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University) ;
  • Kang, Seong-Ho (Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University) ;
  • Han, Hye-Ju (Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University) ;
  • Jang, Young-Saeng (Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University) ;
  • Seo, Goo-Young (Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University) ;
  • Kim, Pyeung-Hyeun (Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University)
  • 투고 : 2013.01.07
  • 심사 : 2013.01.25
  • 발행 : 2013.02.28

초록

Aluminum hydroxide (alum) is the most widely used adjuvant in human vaccines. Nevertheless, it is virtually unknown whether alum acts on B cells. In the present study, we explored the direct effect of alum on Ig expression by murine B cells in vitro. LPS-activated mouse spleen B cells were cultured with alum, and the level of isotype-specific Ig secretion, IgG1 secreting cell numbers, and Ig germ-line transcripts (GLT) were measured using ELISA, ELISPOT, and RT-PCR, respectively. Alum consistently enhanced total IgG1 production, numbers of IgG1 secreting cells, and $GLT{\gamma}1$ expression. These results demonstrate that alum can directly cause IgG1 isotype switching leading to IgG1 production.

키워드

참고문헌

  1. Glenny, A., C. Pope, H. Waddington, and U. Wallace. 1926. The antigenic value of toxoid precipitated by potassium alum. J. Pathol. Bacteriol. 26: 38-39.
  2. Hutchison, S., R. A. Benson, V. B. Gibson, A. H. Pollock, P. Garside, and J. M. Brewer. 2012. Antigen depot is not required for alum adjuvanticity. FASEB J. 26: 1272-1279. https://doi.org/10.1096/fj.11-184556
  3. Munks, M. W., A. S. McKee, M. K. Macleod, R. L. Powell, J. L. Degen, N. A. Reisdorph, J. W. Kappler, and P. Marrack. 2010. Aluminum adjuvants elicit fibrin-dependent extracellular traps in vivo. Blood 116: 5191-5199. https://doi.org/10.1182/blood-2010-03-275529
  4. Kool, M., T. Soullié, M. van Nimwegen, M. A. Willart, F. Muskens, S. Jung, H. C. Hoogsteden, H. Hammad, and B. N. Lambrecht. 2008. Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells. J. Exp. Med. 205: 869-882. https://doi.org/10.1084/jem.20071087
  5. Kool, M., V. Pétrilli, T. De Smedt, A. Rolaz, H. Hammad, M. van Nimwegen, I. M. Bergen, R. Castillo, B. N. Lambrecht, and J. Tschopp. 2008. Cutting edge: alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome. J. Immunol. 181: 3755-3759. https://doi.org/10.4049/jimmunol.181.6.3755
  6. Li, H., S. B. Willingham, J. P. Ting, and F. Re. 2008. Cutting edge: inflammasome activation by alum and alum's adjuvant effect are mediated by NLRP3. J. Immunol. 181: 17-21. https://doi.org/10.4049/jimmunol.181.1.17
  7. Eisenbarth, S. C., O. R. Colegio, W. O'Connor, F. S. Sutterwala, and R. A. Flavell. 2008. Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature 453: 1122-1126. https://doi.org/10.1038/nature06939
  8. Franchi, L. and G. Núñez. 2008. The Nlrp3 inflammasome is critical for aluminium hydroxide-mediated IL-1beta secretion but dispensable for adjuvant activity. Eur. J. Immunol. 38: 2085-2089. https://doi.org/10.1002/eji.200838549
  9. McKee, A. S., M. W. Munks, M. K. MacLeod, C. J. Fleenor, N. Van Rooijen, J. W. Kappler, and P. Marrack. 2009. Alum induces innate immune responses through macrophage and mast cell sensors, but these sensors are not required for alum to act as an adjuvant for specific immunity. J. Immunol. 183: 4403-4414. https://doi.org/10.4049/jimmunol.0900164
  10. Allen, A. C., L. Layward, S. J. Harper, and J. Feehally. 1994. In vitro immunoglobulin isotype suppression in immunoglobulin A nephropathy. Exp. Nephrol. 2: 166-170.
  11. Wang, H. B. and P. F. Weller. 2008. Pivotal advance: eosinophils mediate early alum adjuvant-elicited B cell priming and IgM production. J. Leukoc. Biol. 83: 817-821. https://doi.org/10.1189/jlb.0607392
  12. Shah, H. B., T. S. Devera, P. Rampuria, G. A. Lang, and M. L Lang. 2012. Type II NKT cells facilitate Alum-sensing and humoral immunity. J. Leukoc. Biol. 92: 883-893. https://doi.org/10.1189/jlb.0412177
  13. Peng, S. L. 2005. Signaling in B cells via Toll-like receptors. Curr. Opin. Immunol. 17: 230-236. https://doi.org/10.1016/j.coi.2005.03.003
  14. Nakamura, M., S. Kondo, M. Sugai, M. Nazarea, S. Imamura, and T. Honjo. 1996. High frequency class switching of an IgM+ B lymphoma clone CH12F3 to IgA+ cells. Int. Immunol. 8: 193-201. https://doi.org/10.1093/intimm/8.2.193
  15. Park, S. R., J. H. Lee, and P. H. Kim. 2001. Smad3 and Smad4 mediate transforming growth factor-beta1-induced IgA expression in murine B lymphocytes. Eur. J. Immunol. 31: 1706-1715. https://doi.org/10.1002/1521-4141(200106)31:6<1706::AID-IMMU1706>3.0.CO;2-Z
  16. Gonda, H., M. Sugai, Y. Nambu, T. Katakai, Y. Agata, K. J. Mori, Y. Yokota, and A. Shimizu. 2003. The balance between Pax5 and Id2 activities is the key to AID gene expression. J. Exp. Med. 198: 1427-1437. https://doi.org/10.1084/jem.20030802
  17. Kim, P. H. and M. F. Kagnoff. 1990. Transforming growth factor beta 1 increases IgA isotype switching at the clonal level. J. Immunol. 145: 3773-3778.
  18. Bergstedt-Lindqvist, S., H. B. Moon, U. Persson, G. Möller, C. Heusser, and E. Severinson. 1988. Interleukin 4 instructs uncommitted B lymphocytes to switch to IgG1 and IgE. Eur. J. Immunol. 18: 1073-1077. https://doi.org/10.1002/eji.1830180716
  19. Muramatsu, M., K. Kinoshita, S. Fagarasan, S. Yamada, Y. Shinkai, and T. Honjo. 2000. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102: 553-563. https://doi.org/10.1016/S0092-8674(00)00078-7
  20. Li, S. C., P. B. Rothman, J. Zhang, C. Chan, D. Hirsh, and F. W. Alt. 1994. Expression of I mu-C gamma hybrid germline transcripts subsequent to immunoglobulin heavy chain class switching. Int. Immunol. 6: 491-497. https://doi.org/10.1093/intimm/6.4.491
  21. Kinoshita, K., M. Harigai, S. Fagarasan, M. Muramatsu, and T. Honjo. 2001. A hallmark of active class switch recombination: transcripts directed by I promoters on looped-out circular DNAs. Proc. Natl. Acad. Sci. U. S. A. 98: 12620-12623. https://doi.org/10.1073/pnas.221454398
  22. Revy, P., T. Muto, Y. Levy, F. Geissmann, A. Plebani, O. Sanal, N. Catalan, M. Forveille, R. Dufourcq-Labelouse, A. Gennery, I. Tezcan, F. Ersoy, H. Kayserili, A. G. Ugazio, N. Brousse, M. Muramatsu, L. D. Notarangelo, K. Kinoshita, T. Honjo, A. Fischer, and A. Durandy. 2000. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 102: 565-575. https://doi.org/10.1016/S0092-8674(00)00079-9
  23. Marichal, T., K. Ohata, D. Bedoret, C. Mesnil, C. Sabatel, K. Kobiyama, P. Lekeux, C. Coban, S. Akira, K. J. Ishii, F. Bureau, and C. J. Desmet. 2011. DNA released from dying host cells mediates aluminum adjuvant activity. Nat. Med. 17: 996-1002. https://doi.org/10.1038/nm.2403
  24. Flach, T. L., G. Ng, A. Hari, M. D. Desrosiers, P. Zhang, S. M. Ward, M. E. Seamone, A. Vilaysane, A. D. Mucsi, Y. Fong, E. Prenner, C. C. Ling, J. Tschopp, D. A. Muruve, M. W. Amrein, and Y. Shi. 2011. Alum interaction with dendritic cell membrane lipids is essential for its adjuvanticity. Nat. Med. 17: 479-487. https://doi.org/10.1038/nm.2306

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