Research On The Function Of Orphan Nuclear Receptor Nr4a In Differentiation And Function Of Follicular Helper T Cell

To eliminate antigen, lymphocytes migrate from primary lymphoid organs to the secondary lymphoid organs to initiate immune response. Germinal center(GC) is necessary for the production of high-affinity antibodies to protect bodies from exogenous infection diseases. However, B cell cannot differentiate into GC B cell efficiently and correctly without helper signaling from follicular helper T(Tfh) cells, which were specially located in follicular region. However, the molecular mechanisms that regulate development and function of Tfh cells are not fully understood.In this project, we focused onthe Nr4 a family of orphan nuclear receptors, to study their roles in the differentiation and function of Tfh cells during humoral immune response. Using cell sorting and q PCR method, we firstly found that all members of Nr4 a receptors were significantly highly expressed in Tfh cells. And Nr4 a receptors will immediately upregulate in CD4+ T cells activated in vitro. In a well-established adoptive transfer model, enforced expression of Nr4 a receptors reduces helper T cell expansion but apparently increased the T cell capacity to promote the GC response. On the other hand, deletion of all Nr4 a receptors in T cells did not significantly affect expansion or differentiation of Tfh cells or the d evelopment of GC reaction. These findings suggest Nr4 a receptors may promote but are not necessary for Tfh development or function in vivo.