Chorny, AlejoCasas-Recasens, SandraSintes, JordiShan, MeimeiPolentarutti, NadiaGarcía-Escudero, RamónWalland, A. CooperYeiser, John R.Cassis, LindaCarrillo, JorgePuga, IreneCunha, CristinaBastos, HélderRodrigues, FernandoLacerda, JoãoMorais, AntónioDieguez-Gonzalez, RebecaHeeger, Peter S.Salvatori, GiovanniCarvalho, AgostinhoGarcia-Sastre, AdolfoBlander, J. MagarianMantovani, AlbertoGarlanda, CeciliaCerutti, Andrea2022-11-252022-11-252016J Exp Med. 2016 Sep 19;213(10):2167-21850022-1007http://hdl.handle.net/10451/55249© 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/).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.engjournal article10.1084/jem.201502821540-9538