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On January 12, 2022, Qi Hai's research group from the Institute of Immunology, Tsinghua University published a research paper online in the Journal of Experimental Medicine titled: T-independent antigen induces humoral memory through germinal centers, which revealed the germinal center response The role of polysaccharide antigen in the induction of memory B cells and long-lasting plasmacytopoiesis
.
In the humoral immune response against protein antigens, B cells often undergo high-frequency mutations in the germinal center, undergo T cell screening to produce high-affinity antibodies, and differentiate into memory B cells and long-lasting plasma cells
.
But in response to polysaccharide antigen stimulation, B cells can be activated without the participation of T cells and form an immune memory
.
Based on this phenomenon, a variety of vaccines containing only the capsular polysaccharides of pathogenic bacteria have been produced and widely used, but the mechanism by which polysaccharides stimulate the production of memory B cells and long-acting plasma cells is unclear
.
Polysaccharide antigens can induce the production of T-cell-independent germinal centers, but such germinal centers are short-lived and considered non-functional
.
Through multi-faceted analysis and fate tracking of germinal center B cells induced by polysaccharide antigens, the research team found that although these cells only briefly participated in the germinal center reaction, they could also differentiate into memory B cells and plasma cells, and compared with those with the same Cells with antigen affinity but unable to participate in germinal center responses live longer
.
Young children have weaker humoral immune memory in response to polysaccharide vaccines than adults, making them particularly vulnerable to encapsulated bacteria, a phenomenon similar to that observed in mouse models
.
The research team found that after stimulation with polysaccharide antigens, the B cells of young mice were more difficult to participate in the germinal center response than the adult B cells, although the two types of cells performed equally in the participation of T cells in the germinal center reaction
.
This is one of the reasons why young mouse B cells have difficulty forming memory B cells and long-lasting plasma cells without the help of T cells
.
In conclusion, this study describes a mechanism by which polysaccharide antigens induce the formation of humoral immune memory, implies the programming of immune memory by the germinal center response process itself, and provides theoretical support for the design and optimization of polysaccharide vaccines
.
The study also sheds new light on the need for T cells to respond in the germinal center
.
Professor Qi Hai is the main corresponding author of this paper, assistant researcher Liu Xin is the first author and co-corresponding author of this paper, and doctoral student Zhao Yongshan also made important contributions to the project
.
The research was funded by the Ministry of Science and Technology, the Natural Science Foundation of China, the Tsinghua University-Peking University Life Science Joint Center, the Beijing Municipal Science and Technology Commission, the Center for Frontier Research in Biological Structure, the Gates Foundation, and the Howard Hughes Medical Institute
.
Paper link: https://doi.
org/10.
1084/jem.
20210527 Open for reprinting, welcome to forward to Moments and WeChat groups