Journal article

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



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 ..

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Awarded by National Health and Medical Research Council of Australia

Awarded by European Research Council (LymphoControl for the Busslinger laboratory)

Funding Acknowledgements

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.