Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 213, Issue 10, Pages 2167-2185Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20150282
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Funding
- European Advanced grant [ERC-2011-ADG-20110310]
- Ministerio de Ciencia e Innovacion [SAF2011-25241]
- Marie Curie reintegration grant [PIRG-08-GA-2010-276928]
- Sara Borrell post-doctoral fellowships
- US National Institutes of Health [R01 AI57653, U01AI95613, P01 AI61093, U19 096187]
- Fundacao para a Ciencia e Tecnologia
- Programa Operacional Regional do Norte (ON.2-O Novo Norte)
- Quadro de Referencia Estrategico Nacional through the Fundo Europeu de Desenvolvimento Regional [SFRH/BPD/96176/2013, IF/00735/2014]
- Projeto Estrategico [LA 26 - 2013-2014, PEst-C/SAU/LA0026/2013]
- ICREA Funding Source: Custom
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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.
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