Excessive amounts of mu heavy chain block B-cell development

Int Immunol. 2011 Sep;23(9):545-51. doi: 10.1093/intimm/dxr049. Epub 2011 Jul 4.

Abstract

Antigen-independent B-cell development occurs in several stages that depend on the expression of Ig heavy and light chain. We identified a line of mice that lacked mature B cells in the spleen. This mouse line carried approximately 11 copies of a transgene of the murine heavy chain constant region locus, and B-lineage cells expressed excessive amounts of the intracellular μ heavy chain. B-cell development failed in the bone marrow at the pro/pre B-cell transition, and examination of other lines with various copy numbers of the same transgene suggested that deficiencies in B-cell development increased with increased transgene copy number. Expression of a transgenic (Tg) light chain along with the Tg μ heavy chain led to minimal rescue of B-cell development in the bone marrow and B cells in the spleen. There are several potential mechanisms for the death of pro/pre B cells as a consequence of excess heavy chain expression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Bone Marrow / immunology
  • Cell Differentiation / genetics
  • Cell Lineage / genetics
  • Gene Dosage / genetics
  • Gene Dosage / immunology
  • Immune System / embryology
  • Immune System / growth & development
  • Immune System / pathology*
  • Immunocompetence / genetics
  • Immunoglobulin Light Chains / genetics
  • Immunoglobulin Light Chains / immunology
  • Immunoglobulin Light Chains / metabolism*
  • Immunoglobulin mu-Chains / genetics
  • Immunoglobulin mu-Chains / immunology
  • Immunoglobulin mu-Chains / metabolism*
  • Mice
  • Mice, Transgenic
  • Precursor Cells, B-Lymphoid / immunology
  • Precursor Cells, B-Lymphoid / metabolism*
  • Precursor Cells, B-Lymphoid / pathology
  • Spleen / pathology
  • Transgenes / genetics

Substances

  • Immunoglobulin Light Chains
  • Immunoglobulin mu-Chains