Core Fucosylation of IgG B Cell Receptor Is Required for Antigen Recognition and Antibody Production

Abstract

Ag recognition and Ab production in B cells are major components of the humoral immune response. In the current study, we found that the core fucosylation catalyzed by α1,6-fucosyltransferase (Fut8) was required for the Ag recognition of BCR and the subsequent signal transduction. Moreover, compared with the 3-83 B cells, the coalescing of lipid rafts and Ag-BCR endocytosis were substantially reduced in Fut8-knockdown (3-83-KD) cells with p31 stimulation and then completely restored by reintroduction of the Fut8 gene to the 3-83-KD cells. Indeed, Fut8-null (Fut8−/−) mice evoked a low immune response following OVA immunization. Also, the frequency of IgG-producing cells was significantly reduced in the Fut8−/− spleen following OVA immunization. Our results clearly suggest an unexpected mode of BCR function, in which the core fucosylation of IgG-BCR mediates Ag recognition and, concomitantly, cell signal transduction via BCR and Ab production.

Substrate specificity of FUT8 and chemoenzymatic synthesis of core-fucosylated asymmetric N-glycans

“…4 Another most recent example is that in humoral immune response, core-fucosylation of IgG B cell receptor was shown to mediate antigen recognition and cell signal transduction. 5 Alteration of core-fucosylation is frequently found to be closely related to human diseases including liver cancer, pancreatic cancer, lung cancer, breast cancer, etc. 6 A well-known example is α-fetoprotein, which was found highly core-fucosylated specifically in hepatocellular carcinoma, but not other liver diseases.…”

What Have We Learned from Glycosyltransferase Knockouts in Mice?

“…The loss of the core Fuc on N-glycans of the TGF-β1 receptor correlates with markedly reduced TGF-β signaling via SMAD2, and both cell and lung defects were at least partially rescued by TGF-β. Most recently it has been shown that mice lacking FUT8 exhibit reduced IgG production in response to antigenic stimulation due to a requirement for core Fuc on N-glycans of the IgG-B cell receptor [83]. …”

Core fucosylation of copper transporter 1 plays a crucial role in cisplatin‐resistance of epithelial ovarian cancer by regulating drug uptake

“…Since Fut8 is the sole glycosyltransferase for core fucosylation, the Fut8 −/ − mice, which were generated in our laboratory, were applied here to establish a Fut8 ‐deleted mouse ovarian epithelial cell model . Immunohistochemistry assays with LCA show that core fucosylation was abolished in Fut8 −/− mouse ovary (Figure A).…”

“…Ovary epithelial cells were obtained from homozygous wild type (FUT8 +/+ ), heterozygous (FUT8 +/− ) and Fut‐8 gene‐knockout (FUT8 −/− ) mice . In detail, ovarian tissues were removed from the mice following by incubation in hyaluronidase (100 U) and collagenases (300 U) for 30 min.…”

“…In our previous studies, we found that lack of core fucosylation in transforming growth factor β1 (TGFβ1) receptor and epidermal growth factor receptor results in a marked dysregulation of their activation that is due to a decreased ligand affinity for the receptor . Moreover, core fucosylation of B cell receptor is required for antigen recognition . These findings indicate that core fucosylation is necessary for many molecular interactions on cell membrane.…”