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

Title
The soluble pattern recognition receptor PTX3 links humoral innate and adaptive immune responses by helping marginal zone B cells
Type
Article in International Scientific Journal
Year
2016
Authors
Chorny, A
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Casas Recasens, S
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Sintes, J
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Shan, M
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Polentarutti, N
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Garcia Escudero, R
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Walland, AC
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Yeiser, JR
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Cassis, L
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Carrillo, J
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Puga, I
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Cunha, C
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Bastos, H
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Rodrigues, F
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Lacerda, JF
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Morais, A
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Dieguez Gonzalez, R
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Heeger, PS
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Salvatori, G
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Carvalho, A
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Garcia Sastre, A
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Blander, JM
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Mantovani, A
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Garlanda, C
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Cerutti, A
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Journal
Vol. 213
Pages: 2167-2185
ISSN: 0022-1007
Other information
Authenticus ID: P-00M-3CV
Abstract (EN): 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.
Language: English
Type (Professor's evaluation): Scientific
No. of pages: 19
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