Portal de Periódicos da CAPES

Suppression of B ‐cell activation and I g E , I g A , I g G 1 and I g G 4 production by mammalian telomeric oligonucleotides

2013; Wiley; Volume: 68; Issue: 5 Linguagem: Inglês

10.1111/all.12133

1398-9995

Cansın Saçkesen, Willem van de Veen, Mübeccel Akdiş, Özge Soyer, Judith Zumkehr, Beate Rückert, Barbara Stanić, Ömer Kalaycı, Ş. Ş. Alkan, İhsan Gürsel, Cezmi A. Akdiş,

Immune Cell Function and Interaction

Abstract Background The fine balance of immunoglobulins ( I g) E , I g G 1, I g G 4 and I g A in healthy production is maintained by the interaction of B cells with adaptive and innate immune response. The regulation of toll‐like receptors ( TLR s)‐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 TLR 2, TLR 3, TLR 4, TLR 5, TLR 7, TLR 8 and TLR 9 in the presence or absence of telomeric oligonucleotides. B ‐cell proliferation, differentiation and antibody production were determined. Results TLR 9 ligand directly activates naive and memory B cells, whereas TLR 7 can stimulate them in the presence of plasmacytoid dendritic cells. Human B cells proliferate and turn into antibody‐secreting cells in response to TLR 3, TLR 7 and TLR 9, but not to TLR 2, TLR 4, TLR 5 and TLR 8 ligands. Stimulation of B cells with intracellular TLR 3, TLR 7 and TLR 9 induced an activation cascade leading to memory B ‐cell generation and particularly I g G 1, but also I g A , I g G 4 and very low levels of I g E production. Mammalian telomeric oligodeoxynucleotide ( ODN ) significantly inhibited all features of TLR ligand‐induced events in B cells including B ‐cell proliferation, I g E , I g G 1, I g G 4, I g A production, class switch recombination, plasma cell differentiation induced by TLR 3, TLR 7 and TLR 9 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.