English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

TOSO/FAIM3 recently has been identified as the long-sought-after FcR for IgM (FcμR). FcμR is expressed on human CD19(+) B cells, CD4(+)/CD8(+) T cells, and CD56(+)/CD3(-) NK cells and has been shown to be overexpressed in chronic lymphocytic leukemia (CLL) cells. CLL is a malignancy of mature IgM(+) B lymphocytes that display features of polyreactive, partially anergized B cells related to memory B cells. In this article, we report that FcμR is O-glycosylated in its extracellular domain and identify the major sites of O-glycosylation. By using immunofluorescence confocal microscopy, we found that FcμR localized to the cell membrane but also found that large pools of FcμR accumulate in the trans-Golgi network. Aggregation of FcμR on CLL cells by IgM prompted rapid internalization of both IgM and FcμR, reaching half-maximal internalization of cell-bound IgM within 1 min. Upon internalization, FcμR transported IgM through the endocytic pathway to the lysosome, where it was degraded. Using a series of FcμR deletion mutants, we identified a proline-rich domain essential for cell surface expression of FcμR and a second domain, containing a YXXΦ motif, that controls internalization. Although it has been reported that BCR activation increases FcμR expression, we found that activation of TLRs strongly downregulated FcμR at both the mRNA and protein levels. Through internalization of IgM bound immune complexes, FcμR may play a role in immune surveillance and contribute to B cell activation. In addition, FcμR deserves study as a potential pathway for the delivery of therapeutic Ab-drug conjugates into CLL cells.

the journal of immunology/the journal of immunology

TOSO, the Fcμ Receptor, Is Highly Expressed on Chronic Lymphocytic Leukemia B Cells, Internalizes upon IgM Binding, Shuttles to the Lysosome, and Is Downregulated in Response to TLR Activation