B cell production and turnover in CBA/Ca, CBA/N and CBA/N-bcl-2 transgenic mice: xid-mediated failure among pre B cells is unaltered by bcl-2 overexpression

Curr Top Microbiol Immunol. 2000:252:31-8. doi: 10.1007/978-3-642-57284-5_4.

Abstract

The CBA/N strain carries xid, a murine btk missense mutation that reduces peripheral B cell numbers. Using in vivo BrdU labeling and cytofluorimetry, we have compared the magnitude, production rates, and turnover rates of each B lineage subset in the marrow and periphery of CBA/Ca and CBA/N mice. Our results show the pro-B compartment is largely unaffected by xid. In contrast, the pre-B cell pool is markedly reduced, reflecting a diminished production rate and unaltered turnover time. Despite diminished pre-B cell formation, the size of the immature B cell pool is relatively normal in CBA/N mice, due to increased proportional survival of pre-B cells. In addition, we have assessed the marrow and peripheral B cell subsets of CBA/N mice transgenic for bcl-2. These results indicate that while the bcl-2 transgene promotes lengthened survival in most B cell subsets, the pro/pre-B cell losses mediated by xid are not abrogated by bcl-2 overexpression. Taken together, these findings suggest that the initial [not readable: see text] from the pro- to pre-B cell pools, and that anomalies in subsequent compartments likely reflects the action of homeostatic mechanisms compensating for compromised pre-B cell production.

Publication types

  • Comparative Study

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / pathology*
  • Bone Marrow / pathology
  • Cell Death
  • Cell Differentiation
  • Cell Survival
  • Female
  • Gene Expression Regulation, Developmental
  • Genes, bcl-2*
  • Hematopoiesis / genetics
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / pathology*
  • Homeostasis
  • Humans
  • Immunologic Deficiency Syndromes / enzymology
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / immunology
  • Immunologic Deficiency Syndromes / pathology*
  • Lymphocyte Activation
  • Lymphocyte Count
  • Male
  • Mice
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Mutation, Missense
  • Protein-Tyrosine Kinases / deficiency
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / physiology*
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Spleen / pathology

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • Btk protein, mouse