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

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.