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

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

Data de publicació online: 12/09/2016 Data de publicació en paper: 21 Setembre 2016 Revista: The Journal of Experimental Medicine

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.

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

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