دورية أكاديمية
DC-SIGN binding to mannosylated B-cell receptors in follicular lymphoma down-modulates receptor signaling capacity
| العنوان: | DC-SIGN binding to mannosylated B-cell receptors in follicular lymphoma down-modulates receptor signaling capacity |
|---|---|
| المؤلفون: | Beatriz Valle-Argos, Giorgia Chiodin, Dean J. Bryant, Joe Taylor, Elizabeth Lemm, Patrick J. Duriez, Philip J. Rock, Jonathan C. Strefford, Francesco Forconi, Richard W. Burack, Graham Packham, Freda K. Stevenson |
| المصدر: | Scientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) |
| بيانات النشر: | Nature Portfolio, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Abstract In follicular lymphoma (FL), surface immunoglobulin (sIg) carries mandatory N-glycosylation sites in the variable regions, inserted during somatic hypermutation. These glycosylation sites are tumor-specific, indicating a critical function in FL. Added glycan unexpectedly terminates at high mannose (Mann) and confers capability for sIg-mediated interaction with local macrophage-expressed DC-SIGN lectin resulting in low-level activation of upstream B-cell receptor signaling responses. Here we show that despite being of low-level, DC-SIGN induces a similar downstream transcriptional response to anti-IgM in primary FL cells, characterized by activation of pathways associated with B-cell survival, proliferation and cell–cell communication. Lectin binding was also able to engage post-transcriptional receptor cross-talk pathways since, like anti-IgM, DC-SIGN down-modulated cell surface expression of CXCR4. Importantly, pre-exposure of a FL-derived cell line expressing sIgM-Mann or primary FL cells to DC-SIGN, which does not block anti-IgM binding, reversibly paralyzed the subsequent Ca2+ response to anti-IgM. These novel findings indicate that modulation of sIg function occurs in FL via lectin binding to acquired mannoses. The B-cell receptor alternative engagement described here provides two advantages to lymphoma cells: (i) activation of signaling, which, albeit of low-level, is sufficient to trigger canonical lymphoma-promoting responses, and (ii) protection from exogenous antigen by paralyzing anti-IgM-induced signaling. Blockade of this alternative engagement could offer a new therapeutic strategy. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| العلاقة: | https://doaj.org/toc/2045-2322Test |
| DOI: | 10.1038/s41598-021-91112-7 |
| الوصول الحر: | https://doaj.org/article/0f9b4c5e32fc4b8ab9e5de05992b58d9Test |
| رقم الانضمام: | edsdoj.0f9b4c5e32fc4b8ab9e5de05992b58d9 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20452322 |
|---|---|
| DOI: | 10.1038/s41598-021-91112-7 |