PTX3型
先天免疫系统
免疫系统
生物
获得性免疫系统
免疫学
抗体
模式识别受体
边缘地带
体液免疫
经典补体途径
佐剂
B细胞
炎症
补体系统
作者
Alejo Chorny,Sandra Casas-Recasens,Jordi Sintes,Meimei Shan,Nadia Polentarutti,Ramón García‐Escudero,A. Walland,John R. Yeiser,Linda Cassis,Jorge Carrillo,Irene Puga,Cristina Cunha,Hélder Novais Bastos,Fernando Rodrigues,João F. Lacerda,António Morais,Rebeca Dieguez‐Gonzalez,Peter S. Heeger,Giovanni Salvatori,Agostinho Carvalho
摘要
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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