B cells produce type 1 IFNs in response to the TLR9 agonist CpG-A conjugated to cationic lipids

TY - JOUR

T1 - B cells produce type 1 IFNs in response to the TLR9 agonist CpG-A conjugated to cationic lipids

AU - Akkaya, Munir

AU - Akkaya, Billur

AU - Miozzo, Pietro

AU - Rawat, Mukul

AU - Pena, Mirna

AU - Sheehan, Patrick W.

AU - Kim, Ann S.

AU - Kamenyeva, Olena

AU - Kabat, Juraj

AU - Bolland, Silvia

AU - Chaturvedi, Akanksha

AU - Pierce, Susan K.

N1 - Publisher Copyright: Copyright © 2017 by The American Association of Immunologists, Inc.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - B cells express the innate receptor, 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 IFN in innate immune cells and CpG-B to activating B cells to proliferate and produce Abs 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. In this study we show that both CpG-B and CpG-A activated B cells in vitro to proliferate, secrete Abs 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.

AB - B cells express the innate receptor, 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 IFN in innate immune cells and CpG-B to activating B cells to proliferate and produce Abs 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. In this study we show that both CpG-B and CpG-A activated B cells in vitro to proliferate, secrete Abs 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.

UR - https://www.scopus.com/pages/publications/85026239810

U2 - 10.4049/jimmunol.1700348

DO - 10.4049/jimmunol.1700348

M3 - Article

C2 - 28652397

AN - SCOPUS:85026239810

SN - 0022-1767

VL - 199

SP - 931

EP - 940

JO - Journal of Immunology

JF - Journal of Immunology

IS - 3

ER -