{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMembers of the Fc receptor‐like (FCRL) family participate in fine-tuning B cell responses through diverse mechanisms. One such member, FCRL2, is a transmembrane receptor expressed predominantly by memory B cells. It contains two inhibitory immunoreceptor tyrosine‐based activation motifs (ITIMs) that, upon co‐engagement with the B cell receptor (BCR), become phosphorylated and recruit the Src homology 2 domain–containing phosphatase SHP-1 to attenuate BCR signaling. In this way, FCRL2 acts as a negative immunomodulator controlling B cell activation and maintaining immune homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast, FcRY—a related gene identified via bioinformatics—encodes a protein predicted to consist of three immunoglobulin domains along with a mucin-like region, yet it lacks a classical hydrophobic transmembrane domain. This structural characteristic suggests that FcRY may function as either an intracellular or secreted molecule. Expression of FcRY is observed at low levels across multiple B cell developmental stages and is dynamically regulated; for instance, its expression diminishes following BCR or CD40 signaling but is transiently elevated upon treatment with BAFF/BLyS or LPS. This pattern links FcRY expression to cell cycle status and survival pathways in B cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditionally, the cytosolic proteins FCRLA and FCRLB, which share homology with transmembrane Fc receptor-like proteins, appear to influence antibody responses. Although B cell development and in vitro activation remain largely intact in the absence of FCRLB, its deficiency correlates with enhanced T-dependent antibody responses. This effect is thought to arise from aberrant regulation of the inhibitory receptor FcγRIIb following B cell activation, likely as a consequence of altered promoter function inherited with the mutant Fcrlb allele. Such findings underscore the role of FCRLA/B in modulating B cell effector functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tanisha A Jackson, Christopher L Haga, Götz R A Ehrhardt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FcR-like 2 Inhibition of B cell receptor-mediated activation of B cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1002305"}], "href": "https://doi.org/10.4049/jimmunol.1002305"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21068405"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21068405"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Keiji Masuda, Randall S Davis, Takako Maruyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FcRY, an Fc receptor related gene differentially expressed during B lymphocyte development and activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2005.08.016"}], "href": "https://doi.org/10.1016/j.gene.2005.08.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16263223"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16263223"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Keiji Masuda, Hiromi Mori, Osamu Ohara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Defining the immunological phenotype of Fc receptor-like B (FCRLB) deficient mice: Confounding role of the inhibitory FcγRIIb."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellimm.2010.08.007"}], "href": "https://doi.org/10.1016/j.cellimm.2010.08.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20869045"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20869045"}]}]}]}