The Role And Mechanism Of PKC Theta In The Differentiation And Function Of Follicular Helper T Cells

It is an important physiological process for the body to eliminate pathogenic microorganisms by efficient humoral immune response to external pathogens in order to produce specific and high-affinity neutralizing antibodies.In recent years,studies have shown that follicular helper T cells(TFH)formed by CD4+T cell differentiation can assist germinal center B cell(GC B)selection,formation and differentiation into plasma cells secreting specific and high affinity antibodies.These are the key links of T cell-mediated humoral immune response,the molecular theoretical basis of current vaccine development and the potential therapeutic targets of autoimmune diseases characterized by the increase of autoantibodies.Clarifying the molecular mechanism of follicular helper T cells in formation,differentiation,function and death has essential theoretical significance for vaccine development and disease treatment.Protein kinase C is an effector in the G-protein-coupled receptor system,widely distributed in a variety of tissues,organs and cells.It is a key molecule in the process of cell signaling and plays a key role in glucose metabolism,cell differentiation and gene regulation.Recent studies have found that PKCθ is involved in the differentiation and functional regulation of CD4+T cells toward Th1,Th2,and Th17,but little is known about the differentiation of follicular helper T cells.Therefore,in this study,we used the knockout mouse model to find that PKCθ-/-mice showed serious defects in the differentiation of follicular helper T cells after protein immunization,which resulted in the damage of germinal center of B cells formation,the defect of plasma cell differentiation and antibody secretion.Studies on bone marrow chimera mouse remodeling and adoptive transfer of antigen-specific T cells have found that PKCθ-/-antigen-specific T cells have weakened survival and differentiation ability,impaired proliferation ability,and are more prone to apoptosis.These results reveal the important role of PKCθ in the differentiation of mature CD4+T cells into follicular helper T lymphocytes,and provide an important theoretical support for the future vaccine development and treatment of autoimmune diseases.