Blimp-1Deltaexon7: a naturally occurring Blimp-1 deletion mutant with auto-regulatory potential.
Blimp-1 is a master regulator of terminal B cell differentiation and plays a pivotal role in various developmental processes. In addition to full length Blimp-1, a Blimp-1 mRNA lacking exon 7 (Blimp-1Delta7) has been described to occur in murine B cells. The activity and function of the mutant mRNA-encoded protein (Blimp-1Delta7), lacking three crucial zinc fingers necessary for DNA interaction, is completely unknown. Since isoforms of other prdm family proteins affect each other's functions, we wondered whether Blimp-1Delta7 still plays a role in B cells, independent of direct DNA binding. In this study, we found that Blimp-1Delta7 is preferentially expressed in naïve CD19(+) B cells. A fraction of Blimp-1Delta7 migrates to the nucleus, colocalizes with HDAC2 and is found at sites of repressed chromatin, although it does not bind to the Blimp-1 DNA consensus site. Unexpectedly, Blimp-1 and Blimp-1Delta7 homodimerize as well as heterodimerize with each other. Ectopic expression of Blimp-1Delta7 in WEHI 231 cells, a Blimp-1-negative murine lymphoma line, leads to cessation of proliferation and enhancement of apoptosis. Importantly, LPS-induced differentiation is suppressed in the presence of Blimp-1Delta7. This is in agreement with our finding that Blimp-1Delta7 interferes with endogenous Blimp-1 expression. Thus, our data suggest an auto-regulatory mechanism of Blimp-1 activation.
University of Wuerzburg, Institute for Virology and Immunobiology, Versbacher Strasse 7, 97078, Wuerzburg, Germany.
Doris
D
Schmidt
Arnab
A
Nayak
Julia E
JE
Schumann
Anneliese
A
Schimpl
Ingolf
I
Berberich
Friederike
F
Berberich-Siebelt
D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D019898:Autocrine Communication / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D002478:Cells, Cultured; D005091:Exons; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000074462:Positive Regulatory Domain I-Binding Factor 1; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D014162:Transfection
D018941:Antigens, CD19; D050505:Mutant Proteins; C513258:Prdm1 protein, mouse; D020033:Protein Isoforms; D012333:RNA, Messenger; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1