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J Exp Med. 2016 Sep 19;213(10):2167-85. doi: 10.1084/jem.20150282. Epub 2016 Sep 12.

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

Author information

1
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
2
Program for Inflammatory and Cardiovascular Disorders, Institut Hospital del Mar d'Investigacions Mèdiques, 08003 Barcelona, Spain.
3
Istituto di Ricovero e Cura a Carattere Scientifico Humanitas Clinical and Research Hospital, Rozzano, 20089 Milan, Italy.
4
Molecular Oncology Unit, Centro de Investigaciones Energéticas, Medioambientales, y Tecnológicas, 28040 Madrid, Spain.
5
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029 Institut de Recerca de la Sida IrsiCaixa, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Barcelona, Spain.
6
Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, 4710-057 Braga, Portugal PT Government Associate Laboratory, Braga/Guimarães, Life and Health Sciences Research Institute /3B's, University of Minho, 4710-057 Braga, Portugal.
7
Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, 4710-057 Braga, Portugal PT Government Associate Laboratory, Braga/Guimarães, Life and Health Sciences Research Institute /3B's, University of Minho, 4710-057 Braga, Portugal Serviço de Pneumologia, Centro Hospitalar São João, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal.
8
Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal Hospital de Santa Maria, 1649-035 Lisboa, Portugal.
9
Serviço de Pneumologia, Centro Hospitalar São João, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal.
10
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029 Translational Transplant Research Center and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
11
Sigma-Tau Industrie Farmaceutiche Riunite, Pomezia, 00040 Roma, Italy.
12
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
13
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029 Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
14
Istituto di Ricovero e Cura a Carattere Scientifico Humanitas Clinical and Research Hospital, Rozzano, 20089 Milan, Italy Humanitas University, Rozzano, 20089 Milan, Italy.
15
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029 Program for Inflammatory and Cardiovascular Disorders, Institut Hospital del Mar d'Investigacions Mèdiques, 08003 Barcelona, Spain Catalan Institute for Research and Advanced Studies, 08003 Barcelona, Spain acerutti@imim.es.

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.

PMID:
27621420
PMCID:
PMC5030794
DOI:
10.1084/jem.20150282
[Indexed for MEDLINE]
Free PMC Article

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