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O-GlcNAcylation is required for B cell homeostasis and antibody responses

Author

Listed:
  • Jung-Lin Wu

    (Genomics Research Center, Academia Sinica)

  • Ming-Feng Chiang

    (Genomics Research Center, Academia Sinica)

  • Pan-Hung Hsu

    (National Taiwan Ocean University)

  • Dong-Yen Tsai

    (Genomics Research Center, Academia Sinica
    National Yang-Ming University)

  • Kuo-Hsuan Hung

    (Genomics Research Center, Academia Sinica)

  • Ying-Hsiu Wang

    (Genomics Research Center, Academia Sinica
    National Defense Medical Center)

  • Takashi Angata

    (Academia Sinica)

  • Kuo-I Lin

    (Genomics Research Center, Academia Sinica)

Abstract

O-linked N-acetylglucosamine (O-GlcNAc) transferase (Ogt) catalyzes O-GlcNAc modification. O-GlcNAcylation is increased after cross-linking of the B-cell receptor (BCR), but the physiological function of this reaction is unknown. Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. O-GlcNAcylation of Lyn at serine 19 is crucial for efficient Lyn activation and Syk interaction in BCR-mediated B-cell activation and expansion. Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. Together, these results demonstrate that B cells rely on O-GlcNAcylation to maintain homeostasis, transduce BCR-mediated activation signals and activate humoral immunity.

Suggested Citation

  • Jung-Lin Wu & Ming-Feng Chiang & Pan-Hung Hsu & Dong-Yen Tsai & Kuo-Hsuan Hung & Ying-Hsiu Wang & Takashi Angata & Kuo-I Lin, 2017. "O-GlcNAcylation is required for B cell homeostasis and antibody responses," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01677-z
    DOI: 10.1038/s41467-017-01677-z
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    1. Luis V. Valcárcel & Edurne San José-Enériz & Raquel Ordoñez & Iñigo Apaolaza & Danel Olaverri-Mendizabal & Naroa Barrena & Ana Valcárcel & Leire Garate & Jesús San Miguel & Antonio Pineda-Lucena & Xab, 2024. "An automated network-based tool to search for metabolic vulnerabilities in cancer," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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