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

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 CarvalhoAdolfo Garcia-Sastre, J. Magarian Blander, Alberto Mantovani, Cecilia Garlanda, Andrea Cerutti

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2167-2185
Number of pages19
JournalJournal of Experimental Medicine
Volume213
Issue number10
DOIs
Publication statusPublished - 2016

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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