B Cells Produce Type 1 IFNs in Response to the TLR9 Agonist CpG-A Conjugated to Cationic Lipids.

B Cells Produce Type 1 IFNs in Response to the TLR9 Agonist CpG-A Conjugated to Cationic Lipids.
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DOI:
10.4049/jimmunol.1700348
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发表时间:
2017-08-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Pierce SK
Pierce SK
中科院分区:
其他
文献类型:
--
作者:
Akkaya M;Akkaya B;Miozzo P;Rawat M;Pena M;Sheehan PW;Kim AS;Kamenyeva O;Kabat J;Bolland S;Chaturvedi A;Pierce SK

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B cells express the innate receptor, toll-like receptor 9 (TLR9), which signals in response to unmethylated CpG sequences in microbial DNA. Of the two major classes of CpG-containing oligonucleotides, CpG-A appears restricted to inducing type 1 interferon (type 1 IFN) in innate immune cells and CpG-B to activating B cells to proliferate and produce antibodies and inflammatory cytokines. Although CpGs are candidates for adjuvants to boost innate and adaptive immunity, our understanding of the effect of CpG-A and CpG-B on B cell responses is incomplete. Here we show that both CpG-B and CpG-A activated B cells in vitro to proliferate, secrete antibodies and IL-6 and that neither CpG-B nor CpG-A alone induced type 1 IFN production. However, when incorporated into the cationic lipid, DOTAP, CpG-A, but not CpG-B induced a type 1 IFN response in B cells in vitro and in vivo. We provide evidence that differences in the function of CpG-A and CpG-B may be related to their intracellular trafficking in B cells. These findings fill an important gap in our understanding of the B cell response to CpGs with implications for the use of CpG-A and CpG-B as immunomodulators.
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