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.

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Apoptosis, B-Lymphocyte-Subsets, Bromodeoxyuridine, Cell-Cycle, Cell-Differentiation, Comparative-Study, Female, Gene-Expression-Regulation-Developmental, Hematopoietic-Stem-Cells, Lupus-Erythematosus-Systemic, Mice, Mice-Inbred-BALB-C, Mice-Inbred-C3H, Mice-Inbred-C57BL, Mice-Inbred-NZB, Species-Specificity, SUPPORT-U-S-GOVT-P-H-S

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Dev Immunol 2002 Mar; 9(1):35-45.


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.

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