IMMUNE NETWORK

The Korean Association of Immunobiologists (대한면역학회)
권호 표지
DOI QR코드

DOI QR Code

Newly Identified TLR9 Stimulant, M6-395 Is a Potent Polyclonal Activator for Murine B Cells

  • Park, Mi-Hee (Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University) ;
  • Jung, Yu-Jin (Department of Biological Science, College of Natural Science, Kangwon National University) ;
  • Kim, Pyeung-Hyeun (Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University)
  • Received : 2012.01.03
  • Accepted : 2012.02.20
  • Published : 2012.02.29
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Toll-like receptors (TLRs) have been extensively studied in recent years. However, functions of these molecules in murine B cell biology are largely unknown. A TLR4 stimulant, LPS is well known as a powerful polyclonal activator for murine B cells. Methods: In this study, we explored the effect of a murine TLR9 stimulant, M6-395 (a synthetic CpG ODNs) on B cell proliferation and Ig production. Results: First, M6-395 was much more potent than LPS in augmenting B cell proliferation. As for Ig expression, M6-395 facilitated the expression of both TGF-${\beta}1$-induced germ line transcript ${\alpha}$ ($GLT{\alpha}$) and IL-4-induced $GLT{\gamma}1$ as levels as those by LPS and Pam3CSK4 (TLR1/2 agonist) : a certain Ig GLT expression is regarded as an indicative of the corresponding isotype switching recombination. However, IgA and IgG1 secretion patterns were quite different--these Ig isotype secretions by M6-395 were much less than those by LPS and Pam3CSK4. Moreover, the increase of IgA and IgG1 production by LPS and Pam3CSK4 was virtually abrogated by M6-395. The same was true for the secretion of IgG3. We found that this unexpected phenomena provoked by M6-395 is attributed, at least in part, to its excessive mitogenic nature. Conclusion: Taken together, these results suggest that M6-395 can act as a murine polyclonal activator but its strong mitogenic activity is unfavorable to Ig isotype switching.

Keywords

References

  1. O'Neill LA, Bowie AG: The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol 7;353-364, 2007. https://doi.org/10.1038/nri2079
  2. Latz E, Schoenemeyer A, Visintin A, Fitzgerald KA, Monks BG, Knetter CF, Lien E, Nilsen NJ, Espevik T, Golenbock DT: TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nat Immunol 5;190-198, 2004.
  3. Ehlers M, Fukuyama H, McGaha TL, Aderem A, Ravetch JV: TLR9/MyD88 signaling is required for class switching to pathogenic IgG2a and 2b autoantibodies in SLE. J Exp Med 203;553-561, 2006. https://doi.org/10.1084/jem.20052438
  4. Jegerlehner A, Maurer P, Bessa J, Hinton HJ, Kopf M, Bachmann MF: TLR9 signaling in B cells determines class switch recombination to IgG2a. J Immunol 178;2415-2420, 2007.
  5. Liu N, Ohnishi N, Ni L, Akira S, Bacon KB: CpG directly induces T-bet expression and inhibits IgG1 and IgE switching in B cells. Nat Immunol 4;687-693, 2003. https://doi.org/10.1038/ni941
  6. Choi SS, Chung E, Jung YJ: Newly identified CpG ODNs, M5-30 and M6-395, stimulate mouse immune cells to secrete TNF-alpha and enhance Th1-mediated immunity. J Microbiol 48;512-517, 2010. https://doi.org/10.1007/s12275-010-0053-6
  7. Park SR, Lee JH, Kim PH: Smad3 and Smad4 mediate transforming growth factor-beta1-induced IgA expression in murine B lymphocytes. Eur J Immunol 31;1706-1715, 2001. https://doi.org/10.1002/1521-4141(200106)31:6<1706::AID-IMMU1706>3.0.CO;2-Z
  8. Murray PD, McKenzie DT, Swain SL, Kagnoff MF: Interleukin 5 and interleukin 4 produced by Peyer's patch T cells selectively enhance immunoglobulin A expression. J Immunol 139;2669-2674, 1987.
  9. Hayashi EA, Akira S, Nobrega A: Role of TLR in B cell development: signaling through TLR4 promotes B cell maturation and is inhibited by TLR2. J Immunol 174;6639-6647, 2005. https://doi.org/10.4049/jimmunol.174.11.6639
  10. Yi AK, Chang M, Peckham DW, Krieg AM, Ashman RF: CpG oligodeoxyribonucleotides rescue mature spleen B cells from spontaneous apoptosis and promote cell cycle entry. J Immunol 160;5898-5906, 1998.
  11. Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T: Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102;553-563, 2000. https://doi.org/10.1016/S0092-8674(00)00078-7
  12. Revy P, Muto T, Levy Y, Geissmann F, Plebani A, Sanal O, Catalan N, Forveille M, Dufourcq-Labelouse R, Gennery A, Tezcan I, Ersoy F, Kayserili H, Ugazio AG, Brousse N, Muramatsu M, Notarangelo LD, Kinoshita K, Honjo T, Fischer A, Durandy A: Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 102;565-575, 2000. https://doi.org/10.1016/S0092-8674(00)00079-9
  13. Kim PH, Kagnoff MF: Transforming growth factor beta 1 increases IgA isotype switching at the clonal level. J Immunol 145;3773-3778, 1990.
  14. Berton MT, Uhr JW, Vitetta ES: Synthesis of germ-line gamma 1 immunoglobulin heavy-chain transcripts in resting B cells: induction by interleukin 4 and inhibition by interferon gamma. Proc Natl Acad Sci U S A 86;2829-2833, 1989. https://doi.org/10.1073/pnas.86.8.2829
  15. Stavnezer J: Molecular processes that regulate class switching. Curr Top Microbiol Immunol 245;127-168, 2000.

Cited by

  1. Lactoferrin causes IgA and IgG2b isotype switching through betaglycan binding and activation of canonical TGF-β signaling vol.8, pp.4, 2012, https://doi.org/10.1038/mi.2014.121
  2. In ovo CpG DNA delivery increases innate and adaptive immune cells in respiratory, gastrointestinal and immune systems post-hatch correlating with lower infectious laryngotracheitis virus infection vol.13, pp.3, 2012, https://doi.org/10.1371/journal.pone.0193964