2013 - Strategic Project

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Organizational Unit

Publications

The soluble pattern recognition receptor PTX3 links humoral innate and adaptive immune responses by helping marginal zone B cells

Publication . Chorny, Alejo; Casas-Recasens, Sandra; Sintes, Jordi; Shan, Meimei; Polentarutti, Nadia; García-Escudero, Ramón; Walland, A. Cooper; Yeiser, John R.; Cassis, Linda; Carrillo, Jorge; Puga, Irene; Cunha, Cristina; Bastos, Hélder; Rodrigues, Fernando; Lacerda, João; Morais, António; Dieguez-Gonzalez, Rebeca; Heeger, Peter S.; Salvatori, Giovanni; Carvalho, Agostinho; Garcia-Sastre, Adolfo; Blander, J. Magarian; Mantovani, Alberto; Garlanda, Cecilia; Cerutti, Andrea

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.

2016Journal article

Open access