Journal Article

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

Shi, Wei, Smyth, Gordon K, Nutt, Stephen L, Crawford, Simon, Tellier, Julie, Busslinger, Meinrad, Kallies, Axel, Liao, Yang, Minnich, Martina

2016

نظرة عامة

The transcription factor Blimp-1 is required for the differentiation of activated B cells into plasmablasts. Nutt and colleagues show that plasma cells need Blimp-1 to maintain antibody production by regulating the kinase mTOR and unfolded-protein-response pathways. 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.

• الناشر: Nature Publishing Group US,Nature Publishing Group
• موضوع: 13/31 / 14/28 / 631/250/1619/40/1742 / 631/250/2152/2153/1291 / 64/60 / Activating Transcription Factor 6 - genetics / Activating Transcription Factor 6 - immunology / Animals / Biomedicine / Cell differentiation / Cell Differentiation - immunology / Cell Size / Chromatin Immunoprecipitation / DNA-Binding Proteins - genetics / DNA-Binding Proteins - immunology / Enzyme-Linked Immunosorbent Assay / Flow Cytometry / Gene Expression Profiling / Gene Expression Regulation / Genetic aspects / Genetic transcription / Health aspects / High-Throughput Nucleotide Sequencing / Immune response / Immunoglobulins - immunology / Immunoglobulins - metabolism / Immunology / Infectious Diseases / Interferon Regulatory Factors - genetics / Interferon Regulatory Factors - immunology / Mice / Mice, Knockout / Microscopy, Electron, Transmission / Plasma cells / Plasma Cells - immunology / Plasma Cells - metabolism / Positive Regulatory Domain I-Binding Factor 1 / Properties / Regulation / Regulatory Factor X Transcription Factors / Sequence Analysis, DNA / Survival / TOR Serine-Threonine Kinases - genetics / TOR Serine-Threonine Kinases - immunology / Transcription factors / Transcription Factors - genetics / Transcription Factors - immunology / Unfolded Protein Response - genetics / Unfolded Protein Response - immunology / X-Box Binding Protein 1