The Effect Of PINCH1 On The Function Of Germinal Center B Cells

Germinal center(GCs)are transient structures that generate within peripheral lymphoid organs in response to T cell-dependent antigen.Within GCs,B cells expressing high-affinity antibodies develop.Germinal center B cell undergo VDJ rearrangements,Somatic Hypermutation,Class switch recombination and the selection of affinity mature.Then B cells differentiate to plasma cell and memory B cell.If the differentiation of B cell is abnormal,it can be induced autoimmune disease.Thus it is crucial to regulate the differentiation of B cell.PINCH1 is a family of cell-ECM adhesion proteins,the study found that it plays an important role in integrin signal pathway,cytoskeleton and intracellular important signal pathway include cell adhesion,cell differentiation and apoptosis.Recently study found that PINCH 1 plays an important role in the development of tumor and Nervous system disease.Therefore PINCH1 is a potential therapeutic target.To determine the function of PINCH1 in B cells,we isolated human different phase of B cells from human tonsil.We found that human germinal center B cells express the highest level of PINCH1 among all the B cell subsets analyzed.Then PINCH1 is critical role in germinal center B cell.To detect the function of PINCH 1 in vivo,we got PINCH 1 condition knockout mouse.We used NPCGG to immunized mouse for 12 days.Then we detect the germinal center formation,CSR and antibody-secreting cells.The result show that germinal center formation has not difference but CSR and antibody-secreting cells has significantly increased.We confirm that PINCH1 affect the function of B cell.Then we found that PINCH1 deficiency promoted memory response.Therefore we confirm that PINCH1 regulated the differentiation of GC B cells.