Spi-B inhibits human plasma cell differentiation by repressing BLIMP1 and XBP-1 expression.
The terminal differentiation of B cells into antibody-secreting plasma cells is tightly regulated by a complex network of transcription factors. Here we evaluated the role of the Ets factor Spi-B during terminal differentiation of human B cells. All mature tonsil and peripheral blood B-cell subsets expressed Spi-B, with the exception of plasma cells. Overexpression of Spi-B in CD19(+) B cells inhibited, similar to the known inhibitor BCL-6, the expression of plasma cell-associated surface markers and transcription factors as well as immunoglobulin production, ie, in vitro plasma cell differentiation. The arrest in B-cell differentiation enforced by Spi-B was independent of the transactivation domain, but dependent on the Ets-domain. By chromatin immunoprecipitation and assays using an inducible Spi-B construct BLIMP1 and XBP-1 were identified as direct target genes of Spi-B mediated repression. We propose a novel role for Spi-B in maintenance of germinal center and memory B cells by direct repression of major plasma cell factors and thereby plasma cell differentiation.
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Heike
H
Schmidlin
Sean A
SA
Diehl
Maho
M
Nagasawa
Ferenc A
FA
Scheeren
Remko
R
Schotte
Christel H
CH
Uittenbogaart
Hergen
H
Spits
Bianca
B
Blom
D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000502:physiology; D001665:Binding Sites / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D066298:In Vitro Techniques; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology / Q000502:physiology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D050783:Proto-Oncogene Proteins c-ets / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014161:Transduction, Genetic; D000071717:X-Box Binding Protein 1
D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D050783:Proto-Oncogene Proteins c-ets; D011994:Recombinant Proteins; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1