O-GlcNAcylation is required for B cell homeostasis
and antibody responses
, Ming-Feng Chiang
, Pan-Hung Hsu
, Dong-Yen Tsai
, Kuo-Hsuan Hung
, Ying-Hsiu Wang
& Kuo-I Lin
O-linked N-acetylglucosamine (O-GlcNAc) transferase (Ogt) catalyzes O-GlcNAc modiﬁca-
tion. 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
Genomics Research Center, Academia Sinica, No. 128, Section 2, Academia Road, Nankang District, Taipei 115, Taiwan.
Department of Bioscience and
Biotechnology, National Taiwan Ocean University, No. 2, Beining Road, Jhongjheng District, Keelung 202, Taiwan.
Institute of Biochemistry and Molecular
Biology, National Yang-Ming University, No. 155, Section 2, Linong Street, Beitou District, Taipei 112, Taiwan.
Graduate Institute of Life Sciences, National
Defense Medical Center, No. 161, Section 6, Minquan East Road, Neihu District, Taipei 114, Taiwan.
Institute of Biological Chemistry, Academia Sinica, No.
128, Section 2, Academia Road, Nankang District, Taipei 115, Taiwan. Jung-Lin Wu and Ming-Feng Chiang contributed equally to this work. Correspondence
and requests for materials should be addressed to T.A. (email: email@example.com) or to K.-I.L. (email: firstname.lastname@example.org)