Differential effect of B lymphocyte-induced maturation protein (Blimp-1) expression on cell fate during B cell development.
The B lymphocyte-induced maturation protein (Blimp-1) upregulates the expression of syndecan-1 and J chain and represses that of c-myc. We have transfected Blimp-1 into two sublines of the BCL1 B cell lymphoma that represent distinct stages of B cell development in secondary lymphoid tissues. After interleukin (IL)-2 and IL-5 stimulation, the BCL1 3B3 cells differentiate into centrocyte-like cells, whereas the BCL1 5B1b cells blast and appear to be blocked at the centroblast stage. This blasting effect and the increase in IgM secretion that follows it can be blocked by a dominant negative form of Blimp-1. At the same time, the ectopic expression of Blimp-1 in these partially activated cells induces an apoptotic response that also can be suppressed by the same dominant negative protein. A similar effect was noticed when Blimp-1 was expressed in the mature L10A and the immature WEHI-231 lines, indicating this may be a general effect at earlier stages of the B cell development, and distinct from the ability of Blimp-1 to induce maturation in late stages of differentiation. Truncation mutants indicate that the induction of the apoptotic response relies mainly on 69 amino acids within Blimp-1's proline-rich domain. We propose that Blimp-1 expression defines a checkpoint beyond which fully activated B cells proceed to the plasma cell stage, whereas immature and partially activated cells are eliminated at this point.
Messika
E J
EJ
Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-5428, USA.
Lu
P S
PS
Sung
Y J
YJ
Yao
T
T
Chi
J T
JT
Chien
Y H
YH
Davis
M M
MM
D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology*; D015415:Biomarkers; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured
D015415:Biomarkers; D007376:Interleukin-2; D015848:Interleukin-5; D008934:Mitogens; D012097:Repressor Proteins; D014157:Transcription Factors