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

• Published in: Nature communications Vol. 8; no. 1; pp. 1854 - 10
• Main Authors: Wu, Jung-Lin, Chiang, Ming-Feng, Hsu, Pan-Hung, Tsai, Dong-Yen, Hung, Kuo-Hsuan, Wang, Ying-Hsiu, Angata, Takashi, Lin, Kuo-I
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.11.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/1619/40; 631/250/2152/2153; 631/337/458; Apoptosis; B-cell receptor; Cell activation; Crosslinking; Homeostasis; Humanities and Social Sciences; Humoral immunity; Immune response; Immune system; Immunity; Immunological memory; Lymphocyte receptors; Lymphocytes B; Memory cells; multidisciplinary; N-Acetylglucosamine; O-GlcNAcylation; Science; Science (multidisciplinary); Serine; Signaling; Syk protein; T cell receptors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-01677-z

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. Post-translational modification has a variety of regulatory functions for important immune molecules. Here the authors use B-cell specific knockout mice to show how O -GlcNAcylation is required for functional B cell responses and humoral immunity.