B-cell maturation antigen is modified by a single
            <i>N</i>
            -glycan chain that modulates ligand binding and surface retention

Huang, Hanwen; Chen, Chein‐Hung; Lin, Chung-Wei; Wong, Chi‐Huey; Lin, Kuo‐I

doi:10.1073/pnas.1309417110

Cited by 24 publications

(28 citation statements)

References 47 publications

(59 reference statements)

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“…The differentiation of B cells into plasma cells requires a profound cellular reprograming (58). The prototypical B cell pathways including BCR signaling, and antigen processing and presentation are downregulated; while pathways involved in protein synthesis, N-glycosylation, endoplasmic reticulum (ER) stress and the unfolded protein response are upregulated (59–62). The ER and Golgi systems expand substantially, and metabolic reprogramming supports the secretory demands of the plasma cell: lipid synthesis increases to accommodate organelle remodeling, while glucose uptake and oxidative phosphorylation are upregulated to fuel plasma cell function (61, 63, 64).…”

Section: General Mechanisms Of Humoral Memory In Mice and Humansmentioning

confidence: 99%

Non-classical B Cell Memory of Allergic IgE Responses

et al. 2019

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The long-term effectiveness of antibody responses relies on the development of humoral immune memory. Humoral immunity is maintained by long-lived plasma cells that secrete antigen-specific antibodies, and memory B cells that rapidly respond to antigen re-exposure by generating new plasma cells and memory B cells. Developing effective immunological memory is essential for protection against pathogens, and is the basis of successful vaccinations. IgE responses have evolved for protection against helminth parasites infections and against toxins, but IgE is also a potent mediator of allergic diseases. There has been a dramatic increase in the incidence of allergic diseases in recent decades and this has provided the impetus to study the nature of IgE antibody responses. As will be discussed in depth in this review, the IgE memory response has unique features that distinguish it from classical B cell memory.

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Section: General Mechanisms Of Humoral Memory In Mice and Humansmentioning

confidence: 99%

Non-classical B Cell Memory of Allergic IgE Responses

et al. 2019

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“…1,2,5 Ongoing efforts are focusing on developing more effective immunotherapies targeting selective tumor antigens while simultaneously enhancing immune function in patients. One such selective antigen is B-cell maturation antigen (BCMA), a cell surface glycoprotein 6 and non-tyrosine kinase receptor exclusively expressed on all MM cell lines and patient MM cells at high levels. [7][8][9] It is absent on naïve and memory B cells, but is selectively induced during PC differentiation and supports humoral immunity by promoting survival of plasmablasts and long-lived PCs.…”

Section: Introductionmentioning

confidence: 99%

APRIL and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment

Tai

Acharya

et al. 2016

Blood

265

242

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Here we show that overexpression or activation of B-cell maturation antigen (BCMA) by its ligand, a proliferation-inducing ligand (APRIL), promotes human multiple myeloma (MM) progression in vivo. BCMA downregulation strongly decreases viability and MM colony formation; conversely, BCMA overexpression augments MM cell growth and survival via induction of protein kinase B (AKT), MAPK, and nuclear factor (NF)-κB signaling cascades. Importantly, BCMA promotes in vivo growth of xenografted MM cells harboring p53 mutation in mice. BCMA-overexpressing tumors exhibit significantly increased CD31/microvessel density and vascular endothelial growth factor compared with paired control tumors. These tumors also express increased transcripts crucial for osteoclast activation, adhesion, and angiogenesis/metastasis, as well as genes mediating immune inhibition including programmed death ligand 1, transforming growth factor β, and interleukin 10. These target genes are consistently induced by paracrine APRIL binding to BCMA on MM cells, which is blocked by an antagonistic anti-APRIL monoclonal antibody hAPRIL01A (01A). 01A is cytotoxic against MM cells even in the presence of protective bone marrow (BM) myeloid cells including osteoclasts, macrophages, and plasmacytoid dendritic cells. 01A further decreases APRIL-induced adhesion and migration of MM cells via blockade of canonical and noncanonical NF-κB pathways. Moreover, 01A prevents in vivo MM cell growth within implanted human bone chips in SCID mice. Finally, the effect of 01A on MM cell viability is enhanced by lenalidomide and bortezomib. Taken together, these data delineate new molecular mechanisms of in vivo MM growth and immunosuppression critically dependent on BCMA and APRIL in the BM microenvironment, further supporting targeting this prominent pathway in MM

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“…Recently, different levels of fucosylation have been associated with distinct receptor activities(Huang et al, 2013; Liu et al, 2011), suggesting potential regulatory functions of fucose modification. However, the nature of such regulation remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Negative feedback regulation of Wnt signaling via N-linked fucosylation in zebrafish

Feng

Jiang

et al. 2014

Developmental Biology

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Summary L-fucose, a monosaccharide widely distributed in eukaryotes and certain bacteria, is a determinant of many functional glycans that play central roles in numerous biological processes. The molecular mechanism, however, by which fucosylation mediates these processes remains largely elusive. To study how changes in fucosylation impact embryonic development, we up-regulated N-linked fucosylation via over-expression of a key GDP-Fucose transporter, Slc35c1, in zebrafish. We show that Slc35c1 overexpression causes elevated N-linked fucosylation and disrupts embryonic patterning in a transporter activity dependent manner. We demonstrate that patterning defects associated with enhanced N-linked fucosylation are due to diminished canonical Wnt signaling. Chimeric analyses demonstrate that elevated Slc35c1 expression in receiving cells decreases the signaling range of Wnt8a during zebrafish embryogenesis. Moreover, we provide biochemical evidence that this decrease is associated with degradation of Wnt8 ligand and elevated Lrp6 coreceptor, which we show are both substrates for N-linked fucosylation in zebrafish embryos. Strikingly, slc35c1 expression is regulated by canonical Wnt signaling. These results suggest that Wnt limits its own signaling activity in part via up-regulation of a transporter, slc35c1 that promotes terminal fucosylation and thereby limits Wnt activity.

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B-cell maturation antigen is modified by a single N -glycan chain that modulates ligand binding and surface retention

Cited by 24 publications

References 47 publications

Non-classical B Cell Memory of Allergic IgE Responses

Non-classical B Cell Memory of Allergic IgE Responses

APRIL and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment

Negative feedback regulation of Wnt signaling via N-linked fucosylation in zebrafish

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