Increased frequency of pre-pro B cells in the bone marrow of New Zealand Black (NZB) mice: implications for a developmental block in B cell differentiation.
Reductions in populations of both Pre-B cell (Hardy fractions D) and Pro-B cells (Hardy fractions B-C) have been described in association with murine lupus. Recent studies of B cell populations, based on evaluation of B cell differentiation markers, now allow the enumeration and enrichment of other stage specific precursor cells. In this study we report detailed analysis of the ontogeny of B cell lineage subsets in New Zealand black (NZB) and control strains of mice. Our data suggest that B cell development in NZB mice is partially arrested at the fraction A Pre-Pro B cell stage. This arrest at the Pre-Pro B cell stage is secondary to prolonged lifespan and greater resistance to spontaneous apoptosis. In addition, expression of the gene encoding the critical B cell development transcription factor BSAP is reduced in the Pre-Pro B cell stage in NZB mice. This impairment may influence subsequent B cell development to later stages, and thereby accounts for the down-regulation of the B cell receptor component Ig alpha (mb-1). Furthermore, levels of expression of the Rug2, lambda5 and Ig beta (B29) genes are also reduced in Pre-Pro B cells of NZB mice. The decreased frequency of precursor B cells in the Pre-Pro B cell population occurs at the most primitive stage of B cell differentiation.
D000818:Animals; D017209:Apoptosis; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D013045:Species Specificity
D001973:Bromodeoxyuridine