The research group of Professor Qi Hai of Tsinghua University School of Medicine published a research paper entitled "Follicular T-helper cell recruitment governed by bystander B cells and ICOS-driven motility", which revealed for the first time that ICOS costimulatory molecules directly control the migration of T lymphocytes in vivo The new function of exercise provides new clues for understanding humoral immune regulation. Xu Heping, a doctoral student at Tsinghua University School of Medicine, is the first author of the article.
The humoral immune response is the biological process by which the body produces protective antibodies after infection with pathogens, and is the basis for the role of most protective vaccines. Antibody-producing B lymphocytes do not work independently in the body, but need to obtain signals by interacting with another type of white blood cells (CD4 type helper T lymphocytes), and are called "follicular zone" and "germ center" The lymphatic tissue matures in the microenvironment before it can function. CD4 helper T lymphocytes have several subgroups with different functions. Among them, the special promotion of B cell immune response is called follicular helper T cells, which are distributed in follicular and germinal centers. How such T cells develop is unclear. This issue is one of the focuses of current research on anti-infective immunity and an important subject of cellular immunology. ICOS is a classic T cell costimulatory molecule that can promote T cell activation by activating PI3K signaling. ICOS congenital defects can lead to humoral immunodeficiency (Common Variable Immunodeficiency). Past studies have shown that ICOS is highly expressed on follicular helper T cells. It is generally assumed that ICOS signals may induce T cells to acquire the ability to distribute to follicles and germinal centers by inducing key transcription factors.
By using a variety of genetically engineered mouse models, combined with classical cell immunology methods and two-photon real-time imaging technology in vivo, Qi Hai's research shows that ICOS induces the generation of cell pseudopods through PI3K signaling, promoting the continuity of T cells in vivo Athletic ability. In the follicular area of ​​lymphoid organs, B cells constitutively express ICOS ligands (ICOSL), thereby enabling T cells to migrate to the follicular area effectively by continuously stimulating ICOS signals. Therefore, the ICOS signal can actually directly control the movement ability of T cells in the body and directly determine their migration and distribution in the tissues of the follicular area. These results challenge the prevailing theory of differentiation of follicle-assisted T cell subsets, open up new ways for the study of the relationship between T cell development and microenvironment, and lay the foundation for the use of follicular-assisted T cells to improve antibody vaccines. In addition, because ICOS molecules are involved in many pathological inflammation processes, the new mechanism of ICOS regulating T cell movement also provides new ideas for studying the role of T cell subsets in inflammation.
Professor Qi Hai has been devoted to the study of cell dynamics and regulation in immune response, paying particular attention to the mechanism of multi-cell interaction that is essential for humoral immune protection. This new achievement is another important contribution to his research in the field following the discovery in 2006 by Science that B cells are activated by dendritic cells and in Nature reported in 2008 that SAP molecules regulate TB cell interactions.
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