The soluble pattern recognition receptor PTX3 links humoral innate and adaptive immune responses by helping marginal zone B cells.
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- dc.contributor.author Chorny, Alejoca
- dc.contributor.author Sintes, Jordica
- dc.contributor.author Cassis, Linda, 1977-ca
- dc.contributor.author Puga, Ireneca
- dc.contributor.author Cerutti, Andrea, 1965-ca
- dc.date.accessioned 2017-03-21T11:42:22Z
- dc.date.available 2017-03-21T11:42:22Z
- dc.date.issued 2016
- dc.description.abstract Pentraxin 3 (PTX3) is a fluid-phase pattern recognition receptor of the humoral innate immune system with ancestral antibody-like properties but unknown antibody-inducing function. In this study, we found binding of PTX3 to splenic marginal zone (MZ) B cells, an innate-like subset of antibody-producing lymphocytes strategically positioned at the interface between the circulation and the adaptive immune system. PTX3 was released by a subset of neutrophils that surrounded the splenic MZ and expressed an immune activation-related gene signature distinct from that of circulating neutrophils. Binding of PTX3 promoted homeostatic production of IgM and class-switched IgG antibodies to microbial capsular polysaccharides, which decreased in PTX3-deficient mice and humans. In addition, PTX3 increased IgM and IgG production after infection with blood-borne encapsulated bacteria or immunization with bacterial carbohydrates. This immunogenic effect stemmed from the activation of MZ B cells through a neutrophil-regulated pathway that elicited class switching and plasmablast expansion via a combination of T cell-independent and T cell-dependent signals. Thus, PTX3 may bridge the humoral arms of the innate and adaptive immune systems by serving as an endogenous adjuvant for MZ B cells. This property could be harnessed to develop more effective vaccines against encapsulated pathogens.ca
- dc.description.sponsorship This study was supported by European Advanced grant ERC-2011-ADG-20110310, Ministerio de Ciencia e Innovación grant SAF2011-25241, and Marie Curie reintegration grant PIRG-08-GA-2010-276928 to A. Cerutti; Sara Borrell post-doctoral fellowships to A. Chorny; and US National Institutes of Health grants R01 AI57653, U01 AI95613, P01 AI61093, and U19 096187 to A. Cerutti. C. Cunha and A. Carvalho were funded by grants from Fundação para a Ciência e Tecnologia, co-funded by Programa Operacional Regional do Norte (ON.2—O Novo Norte)., and from the Quadro de Referência Estratégico Nacional (SFRH/BPD/96176/2013 to C. Cunha and grant IF/00735/2014 to A. Carvalho) through the Fundo Europeu de Desenvolvimento Regional and Projeto Estratégico (LA 26 – 2013–2014; PEst-C/SAU/LA0026/2013).
- dc.format.mimetype application/pdfca
- dc.identifier.citation Chorny A, Casas-Recasens S, Sintes J, Shan M, Polentarutti N, García-Escudero R. et al. The soluble pattern recognition receptor PTX3 links humoral innate and adaptive immune responses by helping marginal zone B cells. J Exp Med. 2016 Sep 19;213(10):2167-85. doi: 10.1084/jem.20150282ca
- dc.identifier.doi http://dx.doi.org/10.1084/jem.20150282
- dc.identifier.issn 0022-1007
- dc.identifier.uri http://hdl.handle.net/10230/28269
- dc.language.iso engca
- dc.publisher Rockefeller University Pressca
- dc.relation.ispartof Journal of Experimental Medicine. 2016 Sep 19;213(10):2167-85
- dc.rights Copyright © 2016 Chorny et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri https://creativecommons.org/licenses/by-nc-sa/3.0/ca
- dc.subject.other Sistema immunològicca
- dc.subject.other Anticossosca
- dc.title The soluble pattern recognition receptor PTX3 links humoral innate and adaptive immune responses by helping marginal zone B cells.ca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca