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Suppression of B-cell activation and IgE, IgA, IgG1 and IgG4 production by mammalian telomeric oligonucleotides.
Allergy. 2013; 68(5):593-603.A

Abstract

BACKGROUND

The fine balance of immunoglobulins (Ig) E, IgG1, IgG4 and IgA in healthy production is maintained by the interaction of B cells with adaptive and innate immune response. The regulation of toll-like receptors (TLRs)-driven innate and adaptive immune effector B-cell response and the role of mammalian telomeric TTAGGG repeat elements represent an important research area.

METHODS

Human PBMC and purified naive and memory B cells were stimulated with specific ligands for TLR2, TLR3, TLR4, TLR5, TLR7, TLR8 and TLR9 in the presence or absence of telomeric oligonucleotides. B-cell proliferation, differentiation and antibody production were determined.

RESULTS

TLR9 ligand directly activates naive and memory B cells, whereas TLR7 can stimulate them in the presence of plasmacytoid dendritic cells. Human B cells proliferate and turn into antibody-secreting cells in response to TLR3, TLR7 and TLR9, but not to TLR2, TLR4, TLR5 and TLR8 ligands. Stimulation of B cells with intracellular TLR3, TLR7 and TLR9 induced an activation cascade leading to memory B-cell generation and particularly IgG1, but also IgA, IgG4 and very low levels of IgE production. Mammalian telomeric oligodeoxynucleotide (ODN) significantly inhibited all features of TLR ligand-induced events in B cells including B-cell proliferation, IgE, IgG1, IgG4, IgA production, class switch recombination, plasma cell differentiation induced by TLR3, TLR7 and TLR9 ligands.

CONCLUSION

B cells require specific TLR stimulation, T-cell and plasmacytoid dendritic cell help for distinct activation and Ig production profiles. Host-derived telomeric ODN suppress B-cell activation and antibody production demonstrating a natural mechanism for the control of overexuberant B-cell activation, antibody production and generation of memory.

Authors+Show Affiliations

Swiss Institute of Allergy and Asthma Research SIAF, University of Zurich, CH 7270, Davos, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23480796

Citation

Sackesen, C, et al. "Suppression of B-cell Activation and IgE, IgA, IgG1 and IgG4 Production By Mammalian Telomeric Oligonucleotides." Allergy, vol. 68, no. 5, 2013, pp. 593-603.
Sackesen C, van de Veen W, Akdis M, et al. Suppression of B-cell activation and IgE, IgA, IgG1 and IgG4 production by mammalian telomeric oligonucleotides. Allergy. 2013;68(5):593-603.
Sackesen, C., van de Veen, W., Akdis, M., Soyer, O., Zumkehr, J., Ruckert, B., Stanic, B., Kalaycı, O., Alkan, S. S., Gursel, I., & Akdis, C. A. (2013). Suppression of B-cell activation and IgE, IgA, IgG1 and IgG4 production by mammalian telomeric oligonucleotides. Allergy, 68(5), 593-603. https://doi.org/10.1111/all.12133
Sackesen C, et al. Suppression of B-cell Activation and IgE, IgA, IgG1 and IgG4 Production By Mammalian Telomeric Oligonucleotides. Allergy. 2013;68(5):593-603. PubMed PMID: 23480796.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Suppression of B-cell activation and IgE, IgA, IgG1 and IgG4 production by mammalian telomeric oligonucleotides. AU - Sackesen,C, AU - van de Veen,W, AU - Akdis,M, AU - Soyer,O, AU - Zumkehr,J, AU - Ruckert,B, AU - Stanic,B, AU - Kalaycı,O, AU - Alkan,S S, AU - Gursel,I, AU - Akdis,C A, Y1 - 2013/03/09/ PY - 2013/01/12/accepted PY - 2013/3/14/entrez PY - 2013/3/14/pubmed PY - 2013/10/23/medline SP - 593 EP - 603 JF - Allergy JO - Allergy VL - 68 IS - 5 N2 - BACKGROUND: The fine balance of immunoglobulins (Ig) E, IgG1, IgG4 and IgA in healthy production is maintained by the interaction of B cells with adaptive and innate immune response. The regulation of toll-like receptors (TLRs)-driven innate and adaptive immune effector B-cell response and the role of mammalian telomeric TTAGGG repeat elements represent an important research area. METHODS: Human PBMC and purified naive and memory B cells were stimulated with specific ligands for TLR2, TLR3, TLR4, TLR5, TLR7, TLR8 and TLR9 in the presence or absence of telomeric oligonucleotides. B-cell proliferation, differentiation and antibody production were determined. RESULTS: TLR9 ligand directly activates naive and memory B cells, whereas TLR7 can stimulate them in the presence of plasmacytoid dendritic cells. Human B cells proliferate and turn into antibody-secreting cells in response to TLR3, TLR7 and TLR9, but not to TLR2, TLR4, TLR5 and TLR8 ligands. Stimulation of B cells with intracellular TLR3, TLR7 and TLR9 induced an activation cascade leading to memory B-cell generation and particularly IgG1, but also IgA, IgG4 and very low levels of IgE production. Mammalian telomeric oligodeoxynucleotide (ODN) significantly inhibited all features of TLR ligand-induced events in B cells including B-cell proliferation, IgE, IgG1, IgG4, IgA production, class switch recombination, plasma cell differentiation induced by TLR3, TLR7 and TLR9 ligands. CONCLUSION: B cells require specific TLR stimulation, T-cell and plasmacytoid dendritic cell help for distinct activation and Ig production profiles. Host-derived telomeric ODN suppress B-cell activation and antibody production demonstrating a natural mechanism for the control of overexuberant B-cell activation, antibody production and generation of memory. SN - 1398-9995 UR - https://www.unboundmedicine.com/medline/citation/23480796/Suppression_of_B_cell_activation_and_IgE_IgA_IgG1_and_IgG4_production_by_mammalian_telomeric_oligonucleotides_ L2 - https://doi.org/10.1111/all.12133 DB - PRIME DP - Unbound Medicine ER -