The soluble pattern recognition receptor PTX3 links humoral innate and adaptive immune responses by helping marginal zone B cells.
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.
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Alejo
0000-0001-5874-350X
A
Chorny
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Sandra
0000-0002-5498-3466
S
Casas-Recasens
Program for Inflammatory and Cardiovascular Disorders, Institut Hospital del Mar d'Investigacions Mèdiques, 08003 Barcelona, Spain.
Jordi
J
Sintes
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Meimei
0000-0001-7197-4935
M
Shan
Istituto di Ricovero e Cura a Carattere Scientifico Humanitas Clinical and Research Hospital, Rozzano, 20089 Milan, Italy.
Nadia
N
Polentarutti
Molecular Oncology Unit, Centro de Investigaciones Energéticas, Medioambientales, y Tecnológicas, 28040 Madrid, Spain.
Ramón
0000-0001-5640-6542
R
García-Escudero
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
A Cooper
AC
Walland
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
John R
JR
Yeiser
Program for Inflammatory and Cardiovascular Disorders, Institut Hospital del Mar d'Investigacions Mèdiques, 08003 Barcelona, Spain.
Linda
0000-0003-4544-9816
L
Cassis
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.
Jorge
0000-0003-0221-5948
J
Carrillo
Program for Inflammatory and Cardiovascular Disorders, Institut Hospital del Mar d'Investigacions Mèdiques, 08003 Barcelona, Spain.
Irene
0000-0003-2208-3196
I
Puga
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.
Cristina
C
Cunha
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.
Hélder
0000-0002-1412-4202
H
Bastos
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.
Fernando
0000-0001-8436-9398
F
Rodrigues
Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal Hospital de Santa Maria, 1649-035 Lisboa, Portugal.
João F
JF
Lacerda
Serviço de Pneumologia, Centro Hospitalar São João, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal.
António
0000-0001-8348-8651
A
Morais
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Rebeca
0000-0001-9555-883X
R
Dieguez-Gonzalez
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.
Peter S
0000-0003-4673-6913
PS
Heeger
Sigma-Tau Industrie Farmaceutiche Riunite, Pomezia, 00040 Roma, Italy.
Giovanni
G
Salvatori
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.
Agostinho
0000-0001-8935-8030
A
Carvalho
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Adolfo
0000-0002-6551-1827
A
Garcia-Sastre
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.
J Magarian
JM
Blander
Istituto di Ricovero e Cura a Carattere Scientifico Humanitas Clinical and Research Hospital, Rozzano, 20089 Milan, Italy Humanitas University, Rozzano, 20089 Milan, Italy.
Alberto
0000-0001-5578-236X
A
Mantovani
Istituto di Ricovero e Cura a Carattere Scientifico Humanitas Clinical and Research Hospital, Rozzano, 20089 Milan, Italy Humanitas University, Rozzano, 20089 Milan, Italy.
Cecilia
0000-0002-1510-7703
C
Garlanda
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.
Andrea
A
Cerutti
D056704:Adaptive Immunity; D000328:Adult; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000378:metabolism*; D001419:Bacteria / Q000378:metabolism; D016667:Bacterial Capsules / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D056724:Immunity, Humoral; D007113:Immunity, Innate; D007114:Immunization; D017578:Immunoglobulin Class Switching; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D010950:Plasma Cells / Q000378:metabolism; D011485:Protein Binding; D017452:Receptors, IgG / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000378:metabolism*; D011995:Recombination, Genetic / Q000235:genetics; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D012995:Solubility; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D000099153:Pentraxins
D002097:C-Reactive Protein; D016328:NF-kappa B; D017452:Receptors, IgG; D051192:Receptors, Pattern Recognition; D000683:Serum Amyloid P-Component; D051197:Toll-Like Receptor 4; D000099153:Pentraxins