Pax5/BSAP Maintains the Identity of B Cells in Late B Lymphopoiesis

Horcher, Markus; Souabni, Abdallah; Busslinger, Meinrad

doi:10.1016/s1074-7613(01)00153-4

Cited by 228 publications

(226 citation statements)

References 46 publications

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“…The immunohistological data are, however, conflicting. In the light of the central importance of this transcription factor for maintaining B cell identity but also for preventing B cells from embarking on any non-B lineage developmental programme (Nutt et al, 1999;Horcher et al, 2001) and also of its cellular concentration (Wallin et al, 1998), we assessed PAX-5 expression semi-quantitatively in HRS cells from primary pathological tissues. Using immunohistology, we found expression of PAX-5 in HRS cells in 13/18 (72%) cases of classical HL.…”

Section: Discussionmentioning

confidence: 99%

Loss of B cell identity correlates with loss of B cell-specific transcription factors in Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma

et al. 2002

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In classical Hodgkin lymphoma the malignant Hodgkin/ Reed-Sternberg (HRS) cells characteristically constitute only a small minority of the tumour load. Their origin has been debated for decades, but on the basis of rearrangement and somatic hypermutations of their immunoglubulin (Ig) genes, HRS cells are now ascribed to the B-cell lineage. Nevertheless, phenotypically HRS cells have lost their B cell identity: they usually lack common B cell-specific surface markers such as CD19 and CD79a as well as Ig gene transcripts. Here we demonstrate that Ig promoters as well as both intronic and 3' enhancer sequences are transcriptionally inactive in HRS cell lines. This inactivity correlates with either reduced levels or even a complete lack of several B cellspecific transcription factors required for their expression: Oct-2, OBF-1, PU.1, E47/E12, PAX-5 and EBF. Moreover, we demonstrate that PU.1 and PAX-5 are significantly down-regulated in HRS cells in pathological specimens from primary tumour tissues. However, forced expression of these transcription factors can activate regulatory sequences of silenced B cell marker genes, and in one instance also transcription from a silenced endogenous locus. Thus, HRS cells are dedifferentiated B cells with global down-regulation of B cell-specific genes.

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Section: Discussionmentioning

confidence: 99%

Loss of B cell identity correlates with loss of B cell-specific transcription factors in Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma

et al. 2002

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“…Reverse transcription (with random hexamers) and semiquantitative PCR were performed as described (Horcher et al 2001), using the primers shown in Supplementary Table 3. PCR products were separated on agarose gels and visualized by ethidium bromide.…”

Section: Rt-pcr Analysismentioning

confidence: 99%

Pax5 inducesV-to-DJrearrangements and locus contraction of theimmunoglobulin heavy-chaingene

Fuxa¹,

Skok²,

Souabni³

et al. 2004

Genes Dev.

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“…7,8 Current evidence further indicates that even committed B cells in late lymphopoiesis lose the B-cell phenotype and differentiate into various hematopoietic lineages upon inactivation of PAX5 in mouse B cells. 9 Similarly, it has been shown that different hematopoietic cell types arise from E2A-deficient hematopoietic progenitor cells 10 and recently, that committed B cells transdifferentiated into macrophages after enforced expression of CCAAT enhancer-binding protein (C/EBP) transcription factors in mouse models. 11 Thus, committed mouse B cells can be shown to be plastic by induction of remodeling of the B-cell-specific transcription factor network.…”

Section: Introductionmentioning

confidence: 99%

Aberrant expression of Notch1 interferes with the B-lymphoid phenotype of neoplastic B cells in classical Hodgkin lymphoma

et al. 2008

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Plasticity of committed mouse B cells has been demonstrated by inactivation of the B-cell commitment transcription factor PAX5, resulting in loss of the B-cell phenotype and differentiation into various hematopoietic lineages. Furthermore, mature mouse B cells could be reprogrammed into macrophages by overexpression of myeloid-specific transcription factors. Here, we report that aberrant activity of the transmembrane receptor, Notch1, interferes with the B-lymphoid phenotype of mature human germinal center-derived B cells in Hodgkin lymphoma, so called Hodgkin and Reed-Sternberg cells. They have lost the B-cell phenotype despite their mature B-cell origin. Notch1 remodels the B-cell transcription factor network by antagonizing the key transcription factors E2A and early B-cell factor (EBF). Through this mechanism, B lineage-specific genes were suppressed and B lineage-inappropriate genes were induced. We provide evidence that absence of the Notch inhibitor Deltex1 contributes to deregulated Notch activity in Hodgkin and Reed-Sternberg cells. These data suggest that Notch activation interferes with dedifferentiation of neoplastic B cells in Hodgkin lymphoma.

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Pax5/BSAP Maintains the Identity of B Cells in Late B Lymphopoiesis

Cited by 228 publications

References 46 publications

Loss of B cell identity correlates with loss of B cell-specific transcription factors in Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma

Loss of B cell identity correlates with loss of B cell-specific transcription factors in Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma

Pax5 inducesV-to-DJrearrangements and locus contraction of theimmunoglobulin heavy-chaingene

Aberrant expression of Notch1 interferes with the B-lymphoid phenotype of neoplastic B cells in classical Hodgkin lymphoma

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