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

Z. X. Lian, H. Kita, T. Okada, T. Hsu, L. D. Shultz, K. Dorshkind, A. A. Ansari, S. Ikehara, M. Naiki, M. Eric Gershwin

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9 Scopus citations


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 Igα (mb-1). Furthermore, levels of expression of the Rug2, λ5 and Igβ (B 29) 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.

Original languageEnglish (US)
Pages (from-to)35-45
Number of pages11
JournalDevelopmental Immunology
Issue number1
StatePublished - Mar 2002



  • Autoimmunity
  • B Lymphocytes
  • Lupus
  • New Zealand black mice

ASJC Scopus subject areas

  • Immunology
  • Developmental Biology

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