Role for transcription Pax5A factor in maintaining commitment to the B cell lineage by selective inhibition of granulocyte-macrophage colony-stimulating factor receptor expression.
During early B lymphopoiesis, developing B cells maintain lineage commitment despite the local presence of myeloid lineage-promoting cytokines such as GM-CSF and IL-3. Previous observations suggest that the B cell-specific transcription factor Pax5A (paired box 5A transcription factor) plays a role in maintaining B cell lineage commitment by limiting expansion and survival of early IL-3/GM-CSF-dependent myeloid lineage cells. To define a mechanism by which Pax5A can exert these inhibitory effects on myeloid lineage differentiation, an inducible form of the Pax5A protein was expressed in the myeloid cell line FDC-P1. This cell line models myeloid progenitors in that it responds to the survival and growth-potentiating effects of IL-3 and GM-CSF. We observed that enforced expression of Pax5A selectively suppressed proliferation in response to GM-CSF, but not IL-3. This effect was associated with specific down-regulation of GM-CSFR alpha-chain, but not beta-chain expression. These data provide a molecular mechanism to enforce commitment to the B cell lineage despite the presence of GM-CSF, a factor that has been shown to convert early developing B cells to the myeloid lineage. Furthermore, they indicate a role for B cell Pax5A expression in maintaining rather than directing commitment to the B cell lineage.
Chiang
M Y
MY
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Monroe
J G
JG
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002461:Cell Line, Transformed; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D006131:Growth Inhibitors / Q000235:genetics / Q000502:physiology; D006801:Humans; D007377:Interleukin-3 / Q000037:antagonists & inhibitors / Q000502:physiology; D051379:Mice; D051757:PAX5 Transcription Factor; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D011955:Receptors, Drug / Q000235:genetics / Q000502:physiology; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism; D013629:Tamoxifen / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D007377:Interleukin-3; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; C497282:Pax5 protein, mouse; D011506:Proteins; D011955:Receptors, Drug; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D014157:Transcription Factors; D013629:Tamoxifen; D016178:Granulocyte-Macrophage Colony-Stimulating Factor