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

TitleThe soluble pattern recognition receptor PTX3 links humoral innate and adaptive immune responses by helping marginal zone B cells.
Publication TypeJournal Article
Year of Publication2016
AuthorsChorny, A, Casas-Recasens, S, Sintes, J, Shan, M, Polentarutti, N, GarcĂ­a-Escudero, R, A Walland, C, Yeiser, JR, Cassis, L, Carrillo, J, Puga, I, Cunha, C, Bastos, H, Rodrigues, F, Lacerda, JF, Morais, A, Dieguez-Gonzalez, R, Heeger, PS, Salvatori, G, Carvalho, A, Garcia-Sastre, A, J Blander, M, Mantovani, A, Garlanda, C, Cerutti, A
JournalJ Exp Med
Volume213
Issue10
Pagination2167-85
Date Published2016 Sep 19
ISSN1540-9538
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.

DOI10.1084/jem.20150282
Alternate JournalJ. Exp. Med.
PubMed ID27621420
PubMed Central IDPMC5030794
Grant ListP01 AI061093 / AI / NIAID NIH HHS / United States
R01 AI057653 / AI / NIAID NIH HHS / United States
U01 AI095613 / AI / NIAID NIH HHS / United States