| 2001 |
FCRL5 (IRTA2) encodes a novel cell surface receptor with an ectodomain containing Ig-like domains homologous to Fc and inhibitory receptor families, selectively expressed in mature B cells (centrocytes, marginal zone B cells, and immunoblasts); chromosome 1q21 translocations deregulate IRTA2 expression in tumor cell lines. |
Cloning of chromosomal translocation breakpoints, sequence analysis, expression analysis in B cell lines and tissues |
Immunity |
Medium |
11290337
|
| 2001 |
FCRL5 (BXMAS1) is a cell surface receptor whose expression is transcriptionally induced by anti-IgM crosslinking in B cells; the predicted protein contains 6 Ig-like BXMAS1 domains and 2 cytoplasmic ITIM motifs, with expression restricted to B cells. |
Gene expression analysis after BCR crosslinking, sequence/domain analysis, cell line and tissue expression profiling |
Biochemical and biophysical research communications |
Low |
11453668
|
| 2006 |
Epstein-Barr virus nuclear antigen 2 (EBNA2) markedly induces FcRH5 gene expression in a strictly CBF1-dependent manner; EBNA2 targets CBF1 binding sites in the FcRH5 promoter in vivo, as detected by chromatin immunoprecipitation, and induction does not require other viral proteins or de novo protein synthesis. |
EBNA2 overexpression in CBF1-deficient and wild-type cells, chromatin immunoprecipitation (ChIP) of FcRH5 promoter CBF1 binding sites |
Blood |
High |
16439682
|
| 2012 |
Human FcRL4 and FcRL5 are bona fide Fc receptors: FcRL5 binds all IgG isotypes with varied efficiency, as demonstrated in cellular binding assays; blocking monoclonal antibodies specific for these interactions were generated. |
Cellular binding assays with recombinant FcRL proteins and immunoglobulins; generation of blocking mAbs |
Journal of immunology |
Medium |
22491254
|
| 2012 |
FcRL5 is internalized upon antibody binding on multiple myeloma/plasma cell surfaces, enabling effective antibody-drug conjugate (ADC) delivery; unconjugated anti-FcRL5 antibody alone was not efficacious whereas ADC formats were effective in vitro and in vivo. |
Flow cytometry internalization assay, in vitro cytotoxicity assays, in vivo xenograft mouse models |
Molecular cancer therapeutics |
Medium |
22807577
|
| 2013 |
FCRL5 exerts inhibitory function on BCR signaling in marginal zone (MZ) B cells by recruiting the tyrosine phosphatase SHP-1 to a cytoplasmic ITIM; mutagenesis of the SHP-1 docking site revealed a coactivation function orchestrated by independent association of Lyn Src-family kinase with an intracellular ITAM-like sequence. FCRL5 had no influence on BCR signaling in peritoneal B1 B cells, correlating with differential SHP-1 and Lyn activity between MZ and B1 cells. |
Mutagenesis of ITIM/ITAM-like motifs, BCR signaling assays, SHP-1 and Lyn kinase activity measurements in MZ vs. B1 B cells |
Proceedings of the National Academy of Sciences of the United States of America |
High |
23509253
|
| 2017 |
Anti-FcRH5/CD3 T cell-dependent bispecific antibody (TDB) triggers T cell receptor activation by inducing FcRH5 target clustering and exclusion of CD45 phosphatase from the immune synapse; the membrane-proximal epitope of FcRH5 is required for efficient synapse formation and myeloma cell killing. |
T cell-target cell synapse imaging, CD45 exclusion assay, killing assays with anti-FcRH5/CD3 TDB in human plasma cells and patient-derived myeloma cells, in vivo cynomolgus monkey depletion studies |
Cancer cell |
High |
28262555
|
| 2018 |
CD21 and FCRL5 physically associate to form a receptor complex on B cells; triple engagement of FCRL5, CD21, and BCR produces a superior calcium response compared to CD21+BCR co-stimulation alone. FCRL5 inhibits BCR signaling through its ITIMs in the absence of CD21 stimulation, but CD21 co-engagement converts FCRL5 from a negative to a positive co-receptor. Activating signaling molecules CD19, active PLCγ2, and BTK are rapidly recruited to FCRL5 upon engagement. |
Co-immunoprecipitation, calcium flux assays, signaling molecule recruitment assays in B cell lines and primary tonsil B cells, flow cytometry |
International immunology |
Medium |
30107486
|
| 2023 |
Upregulation of Fcrl5 in B cells disrupts B cell anergy and causes systemic autoimmunity in mice; Fcrl5 overexpression breaks B cell anergy and facilitates toll-like receptor signaling, demonstrated in B cell-specific Fcrl5 transgenic mice. |
B cell-specific Fcrl5 transgenic mouse generation, B cell anergy assays, TLR signaling assays, autoimmune disease model (SLE-like) |
Frontiers in immunology |
Medium |
37841260
|
| 2024 |
Fcrl5 ligation by agonistic antibodies reduces B cell death and enhances proliferation in LPS-stimulated B cells; in the presence of anti-CD40 and IL-5, Fcrl5 ligation suppresses cell death and enhances plasma cell differentiation, thereby promoting humoral immune responses. |
In vitro B cell culture with agonistic anti-Fcrl5 antibodies, cell death/proliferation assays, plasma cell differentiation assays, T cell-dependent and -independent antibody response assays in Fcrl5-overexpressing mice |
International immunology |
Medium |
38738271
|
| 2026 |
Human FcRL5 (but not mouse FcRL5) is a bona fide IgGFc (Fcγ) receptor that uniquely requires two Fcγ molecules in close proximity for robust interaction; cryo-EM reveals FcRL5 engages two Fcγ molecules at a 60° angle, with D1-D2 domains binding the first Fcγ and D3 domain arching over the second Fcγ. FcRL5 can internalize IgG polymers and immune complexes. |
Cryo-electron microscopy, binding assays with IgG immune complexes, internalization assays, species comparison (human vs. mouse FcRL5) |
Science advances |
High |
41477863
|
| 2026 |
Crystal structure of the FCRL5-IgG1 Fc complex at 3.4 Å reveals a 1:1 binding stoichiometry (confirmed by native mass spectrometry and SEC); FCRL5 binds IgG1 Fc in a manner completely distinct from classical Fcγ receptors, explaining why most Fc-silencing mutations do not disrupt FCRL5 binding. Selective cross-linking of FCRL5 with BCR in cis using Fc-engineered antibodies inhibits Ca2+ flux in FCRL5-expressing B cells. |
X-ray crystallography (3.4 Å), native mass spectrometry, size exclusion chromatography, directed evolution of FCRL5 variant, Ca2+ flux assay in B cells, comparison with FcγRIIb co-ligation |
bioRxivpreprint |
High |
42079264
|