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

Munir Akkaya (Lead / Corresponding author), Billur Akkaya, Pietro Miozzo, Mukul Rawat, Mirna Pena, Patrick W. Sheehan, Ann S. Kim, Olena Kamenyeva, Juraj Kabat, Silvia Bolland, Akanksha Chaturvedi, Susan K. Pierce (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)931-940
Number of pages10
JournalJournal of Immunology
Volume199
Issue number3
DOIs
Publication statusPublished - 1 Aug 2017

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'B cells produce type 1 IFNs in response to the TLR9 agonist CpG-A conjugated to cationic lipids'. Together they form a unique fingerprint.

Cite this