PU.1 and Spi-B Are Required for Normal B Cell Receptor–Mediated Signal Transduction

Garrett‐Sinha, Lee Ann; Su, Gloria H.; Rao, Sridhar; Kabak, Shara; Hao, Zengping; Clark, Marcus R.; Simon, M. Celeste

doi:10.1016/s1074-7613(00)80040-0

Cited by 101 publications

(120 citation statements)

References 51 publications

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“…This notion was supported by data presented by Borràs et al 36 However, other data suggested that both PU.1 and Spi-B upregulate gene expression. 37 To our knowledge, this is the first time that Sp1 has been shown to bind at the À1087 position in the human IL-10 promoter. The results of the EMSAs in the present study indicated that Sp1 has a higher affinity for this site than PU.1 and Spi-B.…”

Section: Sp1 Transcription Factor Binds To the Il-10 à1087 G-allele Lmentioning

confidence: 84%

The Sp1 transcription factor binds to the G-allele of the –1087 IL-10 gene polymorphism and enhances transcriptional activation

et al. 2008

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The objectives of this study were to evaluate the influence of the À1087 single nucleotide polymorphism (SNP) on the gene expression of interleukin (IL)-10 and to identify transcription factors binding to this site in B cells. Using electrophoretic mobilityshift assays and nuclear extract from the DG75 B-cell line, we demonstrated that the Sp1 transcription factor bound to the À1087 G-allele of the IL-10 promoter and that the transcription factors PU.1 and Spi-B bound to both the G-and A-alleles. Transient transfections showed that lipopolysaccharide stimulation resulted in a 15-fold increase in promoter activity for the G-allele as compared to a 6-fold increase for the A-allele. Co-transfection with Sp1 expression vector in Sp1-deficient SL2 cells leading to Sp1 binding to the G-allele of the À1087 SNP resulted in increased IL-10 promoter activity. The results suggest a role for Sp1 transcription factor in the activation of IL-10 through the G-allele of the À1087 SNP in response to inflammatory signals.

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Section: Sp1 Transcription Factor Binds To the Il-10 à1087 G-allele Lmentioning

confidence: 84%

The Sp1 transcription factor binds to the G-allele of the –1087 IL-10 gene polymorphism and enhances transcriptional activation

et al. 2008

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“…PU.1 is expressed in multiple hemopoietic lineages, including all stages of B cell development, while the expression of Spi-B is restricted to B cells and T cells (18 -20). Targeted null mutation of Spi-B does not affect B cell development, but results in defective BCR-mediated responses (21,22). Both PU.1 and Spi-B are expressed in the B cell lineage beginning at the pro-B cell stage and appear to interact with identical DNA binding sites (15).…”

Section: Cells (4)mentioning

confidence: 99%

“…Both PU.1 and Spi-B are expressed in the B cell lineage beginning at the pro-B cell stage and appear to interact with identical DNA binding sites (15). Therefore in developing B cells, the available evidence indicates that PU.1 and Spi-B are functionally interchangeable (22,23).…”

Section: Cells (4)mentioning

confidence: 99%

Analysis of Gene Expression and Ig Transcription in PU.1/Spi-B-Deficient Progenitor B Cell Lines

Schweitzer

DeKoter

2004

The Journal of Immunology

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A number of presumptive target genes for the Ets-family transcription factor PU.1 have been identified in the B cell lineage. However, the precise function of PU.1 in B cells has not been studied because targeted null mutation of the PU.1 gene results in a block to lymphomyeloid development at an early developmental stage. In this study, we take advantage of recently developed PU.1−/−Spi-B−/− IL-7 and stromal cell-dependent progenitor B (pro-B) cell lines to analyze the function of PU.1 and Spi-B in B cell development. We show that contrary to previously published expectations, PU.1 and/or Spi-B are not required for Ig H chain (IgH) gene transcription in pro-B cells. In fact, PU.1−/−Spi-B−/− pro-B cells have increased levels of IgH transcription compared with wild-type pro-B cells. In addition, high levels of Igκ transcription are induced after IL-7 withdrawal of wild-type or PU.1−/−Spi-B−/− pro-B cells. In contrast, we found that Igλ transcription is reduced in PU.1−/−Spi-B−/− pro-B cells relative to wild-type pro-B cells after IL-7 withdrawal. These results suggest that Igλ, but not IgH or Igκ, transcription, is dependent on PU.1 and/or Spi-B. The PU.1−/−Spi-B−/− pro-B cells have other phenotypic changes relative to wild-type pro-B cells including increased proliferation, increased CD25 expression, decreased c-Kit expression, and decreased RAG-1 expression. Taken together, our observations suggest that reduction of PU.1 and/or Spi-B activity in pro-B cells promotes their differentiation to a stage intermediate between late pro-B cells and large pre-B cells.

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“…The absence of PU.1 during embryogenesis results in delayed development and reduced numbers of T cells, likely due to the ine cient commitment and/or early di erentiation of T-cell progenitors Spain et al, 1999). Without PU.1, B cells demonstrate marked abnormalities in their B cell mediated signal transduction (Garrett-Sinha et al, 1999). Additionally, terminally di erentiated B cells appear to be absent in PU.1 knockout mice .…”

Section: Ets Transcription Factors In Hematopoiesis Vasculogenesis Amentioning

confidence: 99%

Expression and function of Ets transcription factors in mammalian development: a regulatory network

2000

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PU.1 and Spi-B Are Required for Normal B Cell Receptor–Mediated Signal Transduction

Cited by 101 publications

References 51 publications

The Sp1 transcription factor binds to the G-allele of the –1087 IL-10 gene polymorphism and enhances transcriptional activation

The Sp1 transcription factor binds to the G-allele of the –1087 IL-10 gene polymorphism and enhances transcriptional activation

Analysis of Gene Expression and Ig Transcription in PU.1/Spi-B-Deficient Progenitor B Cell Lines

Expression and function of Ets transcription factors in mammalian development: a regulatory network

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