Roles Of Abp1 In The Development And Function Of Regulatory T Cells And The Effect Of PGRN On B Cell Development And BCR Signal

PART Ⅰ ROLES OF ABP1 IN THE DEVELOPMENT AND FUNCTION OF REGULATORY T CELLSObjective: To explore the effect of Actin-binding protein 1(Abp1)on the development and function of regulatory T cells(Treg).Methods: Detect the proportion,number and related functions of T lymphocytes and Treg cells in the thymus,spleen,superficial lymph nodes and mesenteric lymph nodes of wild-type mice(WT group)and Abp1 knockout mice(KO group)by flow cytometry The expression of sex molecules,and the in vitro inhibition test was used to detect the effect of Abp1 deletion on the inhibitory function of Treg.Result: Compared with WT mice,Abp1 KO mice have no significant changes in the proportion and number of Tregs in the thymus,spleen,superficial lymph nodes and mesenteric lymph nodes.At the same time,the main functional molecules of Treg cells lacking Abp1 ICOS and CTLA4 There is no significant difference in the expression of PD-1 and NRP-1.Further experiments found that Treg cells lacking Abp1 inhibited the differentiation of naive T cells into activated T cells.Compared with WT,the inhibitory effect of Treg cells was not significantly changed.Conclusion: Abp1 has no significant effect on the development and function of Treg cells.PART Ⅱ THE EFFECT OF PGRN ON B CELL DEVELOPMENT AND BCR SIGNALObjective: Explore the potential molecular mechanisms of how PGRN regulates BCR signaling and peripheral B cell differentiation.Methods: The proportion of bone marrow B cells and peripheral B cells of wild-type mice(WT group)and PGRN gene knockout mice(KO group)were detected by flow cytometry.A laser confocal microscope was used to detect the co-localization of p Y,p CD19,p BTK,and p SHIP with BCR.The western blot technique was used to detect the changes of BCR proximal,distal and negative signal molecules.Result: The bone marrow B cases of PGRN KO mice did not change significantly compared with WT mice.The proportion of peripheral B cell subgroup MZ B cells in KO mice increased,while the proportion of GC B cells decreased.The co-localization of p Y,p CD19,p BTK and p SHIP with BCR in the spleen of KO mice was higher than that of WT mice.At the same time,the phosphorylation levels of the BCR upstream signaling molecules CD19,the downstream signaling molecules BTK and PI3 K of CD19,the intermediate and distal signaling molecules FOXO-1,Akt,S6,and the negative BCR signaling molecule SHIP of KO mice are higher than that of WT.high.Conclusion: PGRN has little effect on the early development of B cells,but it is very important for the differentiation of peripheral B cells.The lack of PGRN may enhance the memory immune response,and at the same time enhance the activation of B cells and BCR.