Defective B cell receptor-mediated responses in mice lacking the Ets protein, Spi-B

Su, Gloria H.; Chen, Hui‐Min; Muthusamy, Natarajan; Garrett‐Sinha, Lee Ann; Baunoch, David; Tenen, Daniel G.; Simon, M. Celeste

doi:10.1093/emboj/16.23.7118

Cited by 157 publications

(149 citation statements)

References 80 publications

(115 reference statements)

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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%

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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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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“…Immature B cells demonstrate low level SpiB expression, while immature T cells demonstrate high level expression. In contrast, as these cells mature in the white pulp of the spleen, B cells express high levels, while T cells express much lower levels (Su et al, 1996(Su et al, , 1997.…”

Section: An Overview Of the Expression Patterns Of Ets Family Membersmentioning

confidence: 99%

“…SpiB expression is restricted to the lymphoid lineages, with high levels in B cells and low levels in T cell progenitors (Figure 1) (Chen et al, 1995;Su et al, 1996Su et al, , 1997. SpiB expression decreases during T-cell maturation from the multipotential lymphoid progenitor, but increases markedly with B-cells maturation, suggesting that SpiB plays a key role in di erentiation of lymphoid cell types (Su et al, 1996).…”

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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“…Specifically, Spi-C is expressed in macrophage cell lines, pre-B cell lines, and mature B cell lines, but is not found in pro-B cell lines or Ig ϩ immature B cell lines (30). This pattern of expression partially overlaps the other members of the Spi family, PU.1 and Spi-B, which are expressed throughout B cell development (33)(34)(35). Gel mobility shift analysis shows that Spi-C can bind to PU.1-binding sites in the Ig locus (32).…”

mentioning

confidence: 99%

Spi-C Has Opposing Effects to PU.1 on Gene Expression in Progenitor B Cells

Schweitzer

Huang

Kamath

et al. 2006

The Journal of Immunology

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The Ets transcription factor Spi-C, expressed in B cells and macrophages, is closely related to PU.1 and has the ability to recognize the same DNA consensus sequence. However, the function of Spi-C has yet to be determined. The purpose of this study is to further examine Spi-C activity in B cell development. First, using retroviral vectors to infect PU.1−/− fetal liver progenitors, Spi-C was found to be inefficient at inducing cytokine-dependent proliferation and differentiation of progenitor B (pro-B) cells or macrophages relative to PU.1 or Spi-B. Next, Spi-C was ectopically expressed in fetal liver-derived, IL-7-dependent pro-B cell lines. Wild-type (WT) pro-B cells ectopically expressing Spi-C (WT-Spi-C) have several phenotypic characteristics of pre-B cells such as increased CD25 and decreased c-Kit surface expression. In addition, WT-Spi-C pro-B cells express increased levels of IgH sterile transcripts and reduced levels of expression and transcription of the FcγRIIb gene. Gel-shift analysis suggests that Spi-C, ectopically expressed in pro-B cells, can bind PU.1 consensus sites in the IgH intronic enhancer and FcγRIIb promoter. Transient transfection analysis demonstrated that PU.1 functions to repress the IgH intronic enhancer and activate the FcγRIIb promoter, while Spi-C opposes these activities. WT-Spi-C pro-B cells have reduced levels of dimethylation on lysine 9 of histone H3 within the IgH 3′ regulatory region, indicating that Spi-C can contribute to removal of repressive features in the IgH locus. Overall, these studies suggest that Spi-C may promote B cell differentiation by modulating the activity of PU.1-dependent genes.

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Defective B cell receptor-mediated responses in mice lacking the Ets protein, Spi-B

Abstract: Spi-B is a hematopoietic-specific Ets

Cited by 157 publications

References 80 publications

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

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

Spi-C Has Opposing Effects to PU.1 on Gene Expression in Progenitor B Cells

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