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The engagement of opsonized pathogens by Fc gamma receptors (Fc\u03b3Rs) on neutrophil surfaces mediates multiple antimicrobial functions, including phagocytosis and the production of reactive oxygen species (ROS). Fc\u03b3RIIIb (CD16b) is the most abundant Fc\u03b3R on human neutrophils. This GPI-anchored receptor lacks an intracellular domain. The mechanisms by which Fc\u03b3RIIIb transduce signals remain unclear. A Fc\u03b3RIIIb-deficient phenotype has been reported in apparently healthy adults, which is intriguing given the abundance of this receptor on neutrophil surfaces and its crucial role in neutrophil activation by immune complexes. Here, we identified 2 healthy adult brothers lacking Fc\u03b3RIIIb on neutrophils and characterized their neutrophil activation through Fc\u03b3R engagement by opsonized Escherichia coli. Sequencing of the FCGR3B gene revealed mutations in exon 2 resulting in translation loss. In the absence of stimulation, Fc\u03b3RIIIbnull neutrophils showed unaltered levels of Fc\u03b3RIIa, TLR-2, TLR-4 and TLR-6, but significantly higher Fc\u03b3RIIIa and Fc\u03b3RIa compared to Fc\u03b3RIIIb-expressing controls. Upon challenge with opsonized E. coli, increased surface expression of Fc\u03b3RIa, TLR-4, and \u03b1M integrin (CD11b) was observed exclusively in Fc\u03b3RIIIbnull neutrophils. Antibacterial functions stimulated by opsonized E. coli were significantly lower in Fc\u03b3RIIIbnull neutrophils, including phagocytic capacity and ROS production compared to Fc\u03b3RIIIb-expressing neutrophils. Overall, the absence of Fc\u03b3RIIIb on human neutrophils correlated with impaired antimicrobial functions following stimulation through Fc\u03b3Rs. This study provides new insights into the functional relevance of Fc\u03b3RIIIb and emphasizes the importance of this receptor in neutrophil responses to bacteria.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag066","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T11:46:44Z","timestamp":1779450404000},"source":"Crossref","is-referenced-by-count":1,"title":["Fc\u03b3RIIIb-deficient neutrophils have defects in ROS production, phagocytosis, and actin polymerization following stimulation through Fc\u03b3Rs"],"prefix":"10.1093","volume":"215","author":[{"given":"Jos\u00e9 Antonio","family":"Cruz-C\u00e1rdenas","sequence":"first","affiliation":[{"name":"Escuela de Ingenier\u00eda y Ciencias, Tecnol\u00f3gico de Monterrey , Monterrey, Nuevo Le\u00f3n, M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge Andr\u00e9s","family":"C\u00e1zares-Preciado","sequence":"additional","affiliation":[{"name":"Escuela de Ingenier\u00eda y Ciencias, Tecnol\u00f3gico de Monterrey , Monterrey, Nuevo Le\u00f3n, M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"L\u00f3pez-Arredondo","sequence":"additional","affiliation":[{"name":"Escuela de Ingenier\u00eda y Ciencias, Tecnol\u00f3gico de Monterrey , Monterrey, Nuevo Le\u00f3n, M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Beatriz","family":"S\u00e1nchez-Arg\u00e1ez","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedicine, CINVESTAV-IPN , Av Instituto Polit\u00e9cnico Nacional 2508 , Ciudad de M\u00e9xico,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0269-5884","authenticated-orcid":false,"given":"Michael","family":"Schnoor","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedicine, CINVESTAV-IPN , Av Instituto Polit\u00e9cnico Nacional 2508 , Ciudad de M\u00e9xico,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion E G","family":"Brunck","sequence":"additional","affiliation":[{"name":"Departamento de Inmunolog\u00eda, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico , Ciudad de M\u00e9xico,","place":["Mexico"]},{"name":"The Institute for Obesity Research, Tecnol\u00f3gico de Monterrey , Monterrey, Nuevo Le\u00f3n,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"2026052207450496200_vkag066-B1","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1159\/000360478","article-title":"Phagocytosis and killing of Staphylococcus aureus by human neutrophils","volume":"6","author":"Lu","year":"2014","journal-title":"J Innate 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