Blimp-1 controls plasma cell function through the regulation of immunoglobulin secretion and the unfolded protein response

Nature Immunology
Julie TellierStephen L Nutt

Abstract

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.

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Methods Mentioned

BETA
genotyping
ChIPseq
flow cytometry
protein folding
PCR
RNA-seq
flow
transmission electron microscopy
pulldown

Software Mentioned

limma
featureCounts
Subread aligner
Subjunc aligner

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