IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39734-5.html
   My bibliography  Save this article

Toll-like receptor mediated inflammation directs B cells towards protective antiviral extrafollicular responses

Author

Listed:
  • Jonathan H. Lam

    (University of California Davis
    University of California Davis
    University of California Davis)

  • Nicole Baumgarth

    (University of California Davis
    University of California Davis
    University of California Davis
    Johns Hopkins Bloomberg School of Public Health)

Abstract

Extrafollicular plasmablast responses (EFRs) are considered to generate antibodies of low affinity that offer little protection from infections. Paradoxically, high avidity antigen-B cell receptor engagement is thought to be the main driver of B cell differentiation, whether in EFRs or slower-developing germinal centers (GCs). Here we show that influenza infection rapidly induces EFRs, generating protective antibodies via Toll-like receptor (TLR)-mediated mechanisms that are both B cell intrinsic and extrinsic. B cell-intrinsic TLR signals support antigen-stimulated B cell survival, clonal expansion, and the differentiation of B cells via induction of IRF4, the master regulator of B cell differentiation, through activation of NF-kB c-Rel. Provision of sustained TLR4 stimulation after immunization shifts the fate of virus-specific B cells towards EFRs instead of GCs, prompting rapid antibody production and improving their protective capacity over antigen/alum administration alone. Thus, inflammatory signals act as B cell fate-determinants for the rapid generation of protective antiviral extrafollicular responses.

Suggested Citation

  • Jonathan H. Lam & Nicole Baumgarth, 2023. "Toll-like receptor mediated inflammation directs B cells towards protective antiviral extrafollicular responses," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39734-5
    DOI: 10.1038/s41467-023-39734-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39734-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-39734-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. James D. Phelan & Ryan M. Young & Daniel E. Webster & Sandrine Roulland & George W. Wright & Monica Kasbekar & Arthur L. Shaffer & Michele Ceribelli & James Q. Wang & Roland Schmitz & Masao Nakagawa &, 2018. "A multiprotein supercomplex controlling oncogenic signalling in lymphoma," Nature, Nature, vol. 560(7718), pages 387-391, August.
    2. Sudhir Pai Kasturi & Ioanna Skountzou & Randy A. Albrecht & Dimitrios Koutsonanos & Tang Hua & Helder I. Nakaya & Rajesh Ravindran & Shelley Stewart & Munir Alam & Marcin Kwissa & Francois Villinger &, 2011. "Programming the magnitude and persistence of antibody responses with innate immunity," Nature, Nature, vol. 470(7335), pages 543-547, February.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yandan Yang & Arnold Bolomsky & Thomas Oellerich & Ping Chen & Michele Ceribelli & Björn Häupl & George W. Wright & James D. Phelan & Da Wei Huang & James W. Lord & Callie K. Winkle & Xin Yu & Jan Wis, 2022. "Oncogenic RAS commandeers amino acid sensing machinery to aberrantly activate mTORC1 in multiple myeloma," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Leonardo B. Furstenau & Bruna Rabaioli & Michele Kremer Sott & Danielli Cossul & Mariluza Sott Bender & Eduardo Moreno Júdice De Mattos Farina & Fabiano Novaes Barcellos Filho & Priscilla Paola Severo, 2021. "A Bibliometric Network Analysis of Coronavirus during the First Eight Months of COVID-19 in 2020," IJERPH, MDPI, vol. 18(3), pages 1-24, January.
    3. Bonnie Huang & James D. Phelan & Silvia Preite & Julio Gomez-Rodriguez & Kristoffer H. Johansen & Hirofumi Shibata & Arthur L. Shaffer & Qin Xu & Brendan Jeffrey & Martha Kirby & Stacie Anderson & Yan, 2022. "In vivo CRISPR screens reveal a HIF-1α-mTOR-network regulates T follicular helper versus Th1 cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Joshua Gillard & Madeleine Suffiotti & Peter Brazda & Prashanna B. Venkatasubramanian & Pauline Versteegen & Marien I. Jonge & Dominic Kelly & Sagida Bibi & Marta Valente Pinto & Elles Simonetti & Mih, 2024. "Antiviral responses induced by Tdap-IPV vaccination are associated with persistent humoral immunity to Bordetella pertussis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. Senyu Yao & Xiaoyue Wei & Wenrui Deng & Boyan Wang & Jianye Cai & Yinong Huang & Xiaofan Lai & Yuan Qiu & Yi Wang & Yuanjun Guan & Jiancheng Wang, 2022. "Nestin-dependent mitochondria-ER contacts define stem Leydig cell differentiation to attenuate male reproductive ageing," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39734-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.