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, January 18, 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 response, with Blimp-1 uniquely regulating activity of the kinase mTOR and the size of plasma cells. Thus, Blimp-1 was required for the unique physiological ability of plasma cells that enables the secretion of protective antibody.

Pubmed Link: 26779600

DOI: 10.1038/ni.3348

DOI: 10.1038/ni.3348