ArticleScience translational medicine2013
Allelic-dependent expression of an activating Fc receptor on B cells enhances humoral immune responses.
Article in Science translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 55 citations in OpenAlex.
- Low levels of IgG2 and pneumococcal antibodies as predictors of benefit from IgG replacement in IgG subclass deficiency.Journal of human immunity · 2026Article
- CD177 is a novel IgG Fc receptor and CD177 genetic variants affect IgG-mediated function.Frontiers in immunology · 2024Article
- Improving Antibody Therapeutics by Manipulating the Fc Domain: Immunological and Structural Considerations.Annual review of biomedical engineering · 2022Review
- FCGR3A gene duplication, FcγRIIb-232TT and FcγRIIIb-HNA1a associate with an increased risk of vertical acquisition of HIV-1.PloS one · 2022Article
- FCGR2C: An emerging immune gene for predicting sepsis outcome.Frontiers in immunology · 2022Article
- Relevance of Fc Gamma Receptor Polymorphisms in Cancer Therapy With Monoclonal Antibodies.Frontiers in oncology · 2022Review
- Engineering Anti-Tumor Monoclonal Antibodies and Fc Receptors to Enhance ADCC by Human NK Cells.Cancers · 2021Review
- An HIV Vaccine Protective Allele inFrontiers in immunology · 2021Article
- FcγR Genetic Variation and HIV-1 Vaccine Efficacy: Context And Considerations.Frontiers in immunology · 2021Article
- Article
- Fc Gamma Receptor Polymorphisms Modulated the Vaccine Effect on HIV-1 Risk in the HVTN 505 HIV Vaccine Trial.Journal of virology · 2019Article
- The FCGR2C allele that modulated the risk of HIV-1 infection in the Thai RV144 vaccine trial is implicated in HIV-1 disease progression.Genes and immunity · 2019Article
- Transient and chronic childhood immune thrombocytopenia are distinctly affected by Fc-γ receptor polymorphisms.Blood advances · 2019Article
- Article
- The Ligands for Human IgG and Their Effector Functions.Antibodies (Basel, Switzerland) · 2019Review
- Genetic influences on susceptibility to rheumatoid arthritis in African-Americans.Human molecular genetics · 2019Article
- Type 1 Diabetes Risk in African-Ancestry Participants and Utility of an Ancestry-Specific Genetic Risk Score.Diabetes care · 2019Article
- Mind the Gap: How Interspecies Variability in IgG and Its Receptors May Complicate Comparisons of Human and Non-human Primate Effector Function.Frontiers in immunology · 2019Review
- Multiple Variables at the Leukocyte Cell Surface Impact Fc γ Receptor-Dependent Mechanisms.Frontiers in immunology · 2019Review
- The Human FcγRII (CD32) Family of Leukocyte FcR in Health and Disease.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
B cells are pivotal regulators of acquired immune responses, and recent work in both experimental murine models and humans has demonstrated that subtle changes in the regulation of B cell function can substantially alter immunological responses. The balance of negative and positive signals in maintaining an appropriate B cell activation threshold is critical in B lymphocyte immune tolerance and autoreactivity. FcγRIIb (CD32B), the only recognized Fcγ receptor on B cells, provides immunoglobulin G (IgG)-mediated negative modulation through a tyrosine-based inhibition motif, which down-regulates B cell receptor-initiated signaling. These properties make FcγRIIb a promising target for antibody-based therapy. We report the discovery of allele-dependent expression of the activating FcγRIIc on B cells. Identical to FcγRIIb in the extracellular domain, FcγRIIc has a tyrosine-based activation motif in its cytoplasmic domain. In both human B cells and B cells from mice transgenic for human FcγRIIc, FcγRIIc expression counterbalances the negative feedback of FcγRIIb and enhances humoral responses to immunization in mice and to BioThrax vaccination in a human anthrax vaccine trial. Moreover, the FCGR2C-ORF allele is associated with the risk of development of autoimmunity in humans. FcγRIIc expression on B cells challenges the prevailing paradigm of unidirectional negative feedback by IgG immune complexes via the inhibitory FcγRIIb, is a previously unrecognized determinant in human antibody/autoantibody responses, and opens the opportunity for more precise personalized use of B cell-targeted antibody-based therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.