The transcription factor Blimp1 is not only an essential regulator of plasma cells, but also a risk factor for the development of autoimmune disease. Here, we demonstrate that the mouse Prdm1 (Blimp1) gene was partially activated at the chromatin and transcription level in early B cell development, although mature Prdm1 mRNA did not accumulate due to posttranscriptional regulation. By analyzing a mouse model that facilitated ectopic Blimp1 protein expression throughout B lymphopoiesis, we could demonstrate that Blimp1 impaired B cell development by interfering with the B cell gene expression program, while leading to an increased abundance of plasma cells by promoting premature plasmablast differentiation of immature and mature B cells. With progressive age, these mice developed an autoimmune phenotype characterized by the presence of autoantibodies and glomerulonephritis. Hence, these data identified ectopic Blimp1 expression as a novel mechanism that can explain how Blimp1 as a risk factor contributes to the development of autoimmune disease. SOURCE: Markus Jaritz (markus.jaritz@imp.ac.at) - Busslinger IMP

Pluto Bioinformatics

GSE111692: Precocious expression of Blimp1 in the B cell lineage causes autoimmunity