Emerging Roles for the FCRL Family Members in Lymphocyte Biology and Disease

Li, F. J.; Won, Woong-Jai; Becker, Eugene; Easlick, Juliet; Tabengwa, Edlue M.; Li, R.; Shakhmatov, Mikhail A.; Honjo, Kazuhito; Burrows, Peter D.; Davis, Randall S.

doi:10.1007/978-3-319-07911-0_2

Cited by 41 publications

(55 citation statements)

References 94 publications

(121 reference statements)

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“…4E). The function of FCRL1 and FCRL2 in T REG cells is not known, but given its role in modulating B cell receptor signaling pathway in B cell subsets (Li et al, 2014; Rostamzadeh et al, 2018), where it is highly expressed, it is conceivable that these proteins may module T REG activation and function in a genotype dependent manner. Our data emphasize the importance of studying purified, homogeneous cell types to identify cells and genes most susceptible to the effects of genetic variants.…”

Section: Resultsmentioning

confidence: 99%

Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression

Schmiedel

Singh

Madrigal

et al. 2018

Cell

673

699

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SUMMARY While many genetic variants have been associated with risk for human diseases, how these variants affect gene expression in various cell types remains largely unknown. To address this gap, the DICE (Database of Immune Cell Expression, Expression quantitative trait loci (eQTLs) and Epigenomics) project was established. Considering all human immune cell types and conditions studied, we identified cis-eQTLs for a total of 12,254 unique genes, which represent 61% of all protein-coding genes expressed in these cell types. Strikingly, a large fraction (41%) of these genes showed a strong cis-association with genotype only in a single cell type. We also found that biological sex is associated with major differences in immune cell gene expression in a highly cell-specific manner. These datasets will help reveal the effects of disease risk-associated genetic polymorphisms on specific immune cell types, providing mechanistic insights into how they might influence pathogenesis (http://dice-database.org).

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Section: Resultsmentioning

confidence: 99%

Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression

Schmiedel

Singh

Madrigal

et al. 2018

Cell

673

699

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“…Effector functions arise from the binding of the Fc domain of immunoglobulin G (IgG) to Fcγ receptors (FcγRs) expressed on various leukocyte subsets and also from recruitment of the complement component C1q and the ensuing activation of the classical complement pathway. Human effector FcγRs include, in addition to the well-characterized ‘classical’ (type I) receptors (in humans, FcγRI, FcγRII, FcγRIII and their isoforms), the lectin-like type II receptors (CD23 and CD209), TRIM21 and members of the FCRL family of receptors 3,4 . The recruitment and signaling of type I receptors via immunocomplexes (ICs) are responsible for antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellmediated phagocytosis (ADCP), reactions that have been established clinically to contribute to the mechanism of action of many therapeutic antibodies 5 .…”

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confidence: 99%

IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions

et al. 2017

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Engineered crystallizable fragment (Fc) regions of antibody domains, which assume a unique and unprecedented asymmetric structure within the homodimeric Fc polypeptide, enable completely selective binding to the complement component C1q and activation of complement via the classical pathway without any concomitant engagement of the Fcγ receptor (FcγR). We used the engineered Fc domains to demonstrate in vitro and in mouse models that for therapeutic antibodies, complement-dependent cell-mediated cytotoxicity (CDCC) and complement-dependent cell-mediated phagocytosis (CDCP) by immunological effector molecules mediated the clearance of target cells with kinetics and efficacy comparable to those of the FcγR-dependent effector functions that are much better studied, while they circumvented certain adverse reactions associated with FcγR engagement. Collectively, our data highlight the importance of CDCC and CDCP in monoclonal-antibody function and provide an experimental approach for delineating the effect of complement-dependent effector-cell engagement in various therapeutic settings.

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“…FCRL4 and FCRL5 are true FcRs because they bind Ig. FCRL4 binds IgA, whereas FCRL5 binds all subclasses of IgG albeit with different affinities (65,69). In contrast FCRL6, which contains a CYT with a consensus ITIM and atypical ITAM, is expressed on NK cells and mature CTL, including the rare population of CD4 + CTL that lyses target cells in a MHC class II-restricted manner.…”

Section: Discussionmentioning

confidence: 99%

A Leukocyte Immune-Type Receptor Subset Is a Marker of Antiviral Cytotoxic Cells in Channel Catfish, Ictalurus punctatus

Taylor

Moulana

Stuge

et al. 2016

The Journal of Immunology

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Channel catfish, Ictalurus punctatus, leukocyte immune type receptors (LITRs) represent a multigene family that encodes Ig superfamily proteins that mediate activating or inhibitory signaling. In this study, we demonstrate the use of mAb CC41 to monitor viral cytotoxic responses in catfish and determine that CC41 binds to a subset of LITRs on the surface of catfish clonal CTLs. Homozygous gynogenetic catfish were immunized with channel catfish virus (CCV)–infected MHC-matched clonal T cells (G14D-CCV), and PBL were collected at various times after immunization for flow cytometric analyses. The percentage of CC41+ cells was significantly increased 5 d after primary immunization with G14D-CCV and at 3 d after a booster immunization as compared with control fish only injected with G14D. Moreover, CC41+ cells magnetically isolated from the PBL specifically killed CCV-infected targets as measured by 51Cr release assays and expressed messages for CD3γδ, perforin, and at least one of the CD4-like receptors as analyzed by RNA flow cytometry. When MLC effector cells derived from a G14D-CCV–immunized fish were preincubated with CC41 mAb, killing of G14D-CCV targets was reduced by ∼40%, suggesting that at least some LITRs have a role in target cell recognition and/or cytotoxicity. The availability of a LITR-specific mAb has allowed, to our knowledge for the first time, functional characterization of LITRs in an autologous system. In addition, the identification of an LITR subset as a cytotoxic cell marker will allow for more effective monitoring of catfish immune responses to pathogens.

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Emerging Roles for the FCRL Family Members in Lymphocyte Biology and Disease

Cited by 41 publications

References 94 publications

Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression

Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression

IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions

A Leukocyte Immune-Type Receptor Subset Is a Marker of Antiviral Cytotoxic Cells in Channel Catfish, Ictalurus punctatus

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