Expression of a V region-less B cell receptor confers a tolerance-like phenotype on transgenic B cells

J Immunol. 2001 Mar 1;166(5):3083-9. doi: 10.4049/jimmunol.166.5.3083.

Abstract

Neoplastic B cells from H chain disease patients express a truncated B cell receptor (BCR), comprising a membrane Ig that lacks part of its extracellular domain. It has been speculated that deletion of the Ag binding domain would confer a constitutive activity on the BCR, as it has been shown for oncogenic growth factor receptors. A V region-less BCR has constitutive activity, because in transgenic mice it causes inhibition of endogenous H chain gene rearrangements and relieves the requirement for surrogate L chain in pre-B cell development. However, it has been speculated that normal Ag receptors also display constitutive activity. Here we show that transgenic B cells expressing a membrane H chain disease protein on their surface are phenotypically and functionally similar to B cells developing in the presence of their cognate Ag and that cells with normal levels of mutant BCR are eliminated in spleen via a bcl-2 sensitive pathway while progressing toward the mature stage. In contrast, cells with lower levels of mutant receptors develop as mature B cells. These findings support the view that the truncated BCR has a constitutive activity that mimics ligand binding, in analogy to what has been shown for oncogenic growth factor receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / immunology
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism*
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Clonal Anergy / genetics
  • Crosses, Genetic
  • Gene Rearrangement, B-Lymphocyte, Light Chain
  • Humans
  • Immune Tolerance / genetics*
  • Immunoglobulin Light Chains / biosynthesis
  • Immunoglobulin Light Chains / genetics
  • Immunoglobulin mu-Chains / biosynthesis
  • Immunoglobulin mu-Chains / genetics
  • Immunophenotyping
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • Receptors, Antigen, B-Cell / biosynthesis*
  • Receptors, Antigen, B-Cell / deficiency
  • Receptors, Antigen, B-Cell / genetics*
  • T-Lymphocytes / immunology
  • Transgenes / immunology*

Substances

  • Immunoglobulin Light Chains
  • Immunoglobulin mu-Chains
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Antigen, B-Cell