Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program.

Shaffer AL, Lin KI, Kuo TC, Yu X, Hurt EM, Rosenwald A, Giltnane JM, Yang L, Zhao H, Calame K, Staudt LM
Immunity. 2002 17 (1): 51-62

PMID: 12150891 · DOI:10.1016/s1074-7613(02)00335-7

Blimp-1, a transcriptional repressor, drives the terminal differentiation of B cells to plasma cells. Using DNA microarrays, we found that introduction of Blimp-1 into B cells blocked expression of a remarkably large set of genes, while a much smaller number was induced. Blimp-1 initiated this cascade of gene expression changes by directly repressing genes encoding several transcription factors, including Spi-B and Id3, that regulate signaling by the B cell receptor. Blimp-1 also inhibited immunoglobulin class switching by blocking expression of AID, Ku70, Ku86, DNA-PKcs, and STAT6. These findings suggest that Blimp-1 promotes plasmacytic differentiation by extinguishing gene expression important for B cell receptor signaling, germinal center B cell function, and proliferation while allowing expression of important plasma cell genes such as XBP-1.

MeSH Terms (24)

Animals Base Sequence Binding Sites Cell Differentiation Cell Line DNA-Binding Proteins Gene Expression Profiling Gene Expression Regulation Humans Immunoglobulin Class Switching Mice Models, Immunological Oligonucleotide Array Sequence Analysis Plasma Cells Positive Regulatory Domain I-Binding Factor 1 Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-6 Receptors, Antigen, B-Cell Repressor Proteins RNA, Messenger Signal Transduction Spleen Transcription Factors Tumor Cells, Cultured

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