Blimp-1 controls plasma cell function through the regulation of immunoglobulin secretion and the unfolded protein response
Julie Tellier, Wei Shi, Martina Minnich, Yang Liao, Simon Crawford, Gordon K Smyth, Axel Kallies, Meinrad Busslinger, Stephen L Nutt
NATURE IMMUNOLOGY | NATURE PUBLISHING GROUP | Published : 2016
Plasma cell differentiation requires silencing of B cell transcription, while it establishes antibody-secretory function and long-term survival. The transcription factors Blimp-1 and IRF4 are essential for the generation of plasma cells; however, their function in mature plasma cells has remained elusive. We found that while IRF4 was essential for the survival of plasma cells, Blimp-1 was dispensable for this. Blimp-1-deficient plasma cells retained their transcriptional identity but lost the ability to secrete antibody. Blimp-1 regulated many components of the unfolded protein response (UPR), including XBP-1 and ATF6. The overlap in the functions of Blimp-1 and XBP-1 was restricted to that ..View full abstract
Awarded by National Health and Medical Research Council of Australia
Awarded by European Research Council (LymphoControl for the Busslinger laboratory)
We thank U. Klein (Columbia University) for Irf4<SUP>fl/fl</SUP>; L. Glimcher (Weill Cornell Medical College) for Xbp1<SUP>fl/fl</SUP> mice; S. Wilcox, M. Chopin and C. Seillet for technical assistance; and J. Leahy for animal care. Supported by the National Health and Medical Research Council of Australia (G.K.S. and S.L.N.; 361646, 575500 and 1054925 to S.L.N.; 1054618 to G.K.S.; 1023454 to G.K.S. and W.S.; and 1049416 to A.K.), the Sylvia and Charles Viertel Foundation (A.K.), the Multiple Myeloma Research Foundation (S.L.N.), Boehringer Ingelheim (Busslinger laboratory) and the European Research Council (291740-LymphoControl for the Busslinger laboratory), and made possible through Victorian State Government Operational Infrastructure Support.