Type I interferon promotes the fate of Toll-like receptor 9–stimulated follicular B cells to plasma cell differentiation

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  • Ryota Higuchi
    Division of Immunology and Genome Biology, Medical Institute of Bioregulation, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 , Japan
  • Kaori Tanaka
    Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 , Japan
  • Yuichi Saito
    Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 , Japan
  • Daisuke Murakami
    Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 , Japan
  • Takashi Nakagawa
    Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 , Japan
  • Stephen L Nutt
    The Walter and Eliza Hall Institute of Medical Research , Parkville, VIC 3050 , Australia
  • Yasuyuki Ohkawa
    Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 , Japan
  • Yoshihiro Baba
    Division of Immunology and Genome Biology, Medical Institute of Bioregulation, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 , Japan
  • Hidde Ploegh
    editor

Bibliographic Information

Published
2024-03-28
Resource Type
journal article
Rights Information
  • https://creativecommons.org/licenses/by/4.0/
DOI
  • 10.1093/pnasnexus/pgae152
Publisher
Oxford University Press (OUP)

Description

<jats:title>Abstract</jats:title> <jats:p>The activation and differentiation of B cells into plasma cells (PCs) play critical roles in the immune response to infections and autoimmune diseases. Toll-like receptor 9 (TLR9) responds to bacterial and viral DNA containing unmethylated CpG motifs and triggers immune responses in B cells; however, abnormal recognition of self-DNA by TLR9 can cause autoimmune diseases. When stimulated with TLR9 agonists, follicular (FO) B cells, a subset of B cells residing in the FO regions of secondary lymphoid organs, exhibit a propensity for activation but fail to give rise to PCs. The factors that enable the transition of TLR9-activated FO B cells from activation to differentiation into PCs remain unclear. In this study, we show that type I interferon-alpha (IFNα) signaling causes FO B cells activated by CpG stimulation to differentiate into PCs. Although CpG stimulation alone only temporarily increased interferon regulatory factor 4 (IRF4) expression in FO B cells, co-stimulation with both CpG and IFNα enhanced and maintained high IRF4 expression levels, ultimately enabling the cells to differentiate into PCs. Overexpression of IRF4 in FO B cells results in CpG-induced PC transition without IFN signaling. Furthermore, co-stimulation of TLR9 and IFNα receptors significantly enhanced mammalian target of rapamycin (mTOR) signaling, which regulates IRF4 expression and PC generation. These findings suggest that IFNα may play a key role in promoting the fate of PC differentiation in FO B cells activated by TLR9 stimulation.</jats:p>

Journal

  • PNAS Nexus

    PNAS Nexus 3 (4), 2024-03-28

    Oxford University Press (OUP)

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