A B Cell-Deficient Mouse by Targeted Disruption of the Membrane Exon of the Immunoglobulin Mu Chain Gene

Nature. 1991 Apr 4;350(6317):423-6. doi: 10.1038/350423a0.

Abstract

Of the various classes of antibodies that B lymphocytes can produce, class M (IgM) is the first to be expressed on the membrane of the developing cells. Pre-B cells, the precursors of B-lymphocytes, produce the heavy chain of IgM (mu chain), but not light chains. Recent data suggest that pre-B cells express mu chains on the membrane together with the 'surrogate' light chains lambda 5 and V pre B (refs 2-7). This complex could control pre-B-cell differentiation, in particular the rearrangement of the light-chain genes. We have now assessed the importance of the membrane form of the mu chain in B-cell development by generating mice lacking this chain. We disrupted one of the membrane exons of the gene encoding the mu-chain constant region by gene targeting in mouse embryonic stem cells. From these cells we derived mice heterozygous or homozygous for the mutation. B-cell development in the heterozygous mice seemed to be normal, but in homozygous animals B cells were absent, their development already being arrested at the stage of pre-B-cell maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation, B-Lymphocyte / analysis
  • B-Lymphocytes / physiology*
  • Blotting, Southern
  • DNA Mutational Analysis
  • Flow Cytometry
  • Genes, Immunoglobulin*
  • Hematopoiesis
  • Immunoglobulin Light Chains
  • Immunoglobulin Light Chains, Surrogate
  • Immunoglobulin mu-Chains / genetics*
  • Immunologic Deficiency Syndromes / genetics*
  • Membrane Glycoproteins / genetics
  • Mice
  • Receptors, Antigen, B-Cell / genetics*

Substances

  • Antigens, Differentiation, B-Lymphocyte
  • Immunoglobulin Light Chains
  • Immunoglobulin Light Chains, Surrogate
  • Immunoglobulin mu-Chains
  • Membrane Glycoproteins
  • Receptors, Antigen, B-Cell