Ig-alpha cytoplasmic truncation renders immature B cells more sensitive to antigen contact

Immunity. 1999 Nov;11(5):537-45. doi: 10.1016/s1074-7613(00)80129-6.

Abstract

To study the function of Ig-alpha in the selection of autoreactive B cells, we have analyzed mb-1 cytoplasmic truncation mutant mice (mb-1delta(c)/delta(c)), which coexpress transgenes encoding hen egg lysozyme (HEL) and HEL-specific immunoglobulin. We demonstrate that in the presence of soluble HEL (sHEL) and dependent on the mb-1delta(c) mutation, most immature B cells bearing the HEL-specific Ig transgene undergo rearrangements of endogenous kappa light chains, resulting in loss of HEL specificity. Moreover, immature B cells from Ig-alpha mutant mice respond to BCR cross-linking with an exaggerated and prolonged calcium response and induction of protein tyrosine phosphorylation. Our data imply a negative signaling role for Ig-alpha in immature B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Specificity
  • Antigens, CD / chemistry*
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Apoptosis
  • Autoantigens / genetics
  • Autoantigens / immunology*
  • CD79 Antigens
  • Calcium Signaling / immunology*
  • Clonal Deletion
  • Crosses, Genetic
  • Gene Rearrangement, B-Lymphocyte, Light Chain
  • Immunoglobulin kappa-Chains / immunology
  • Immunologic Capping
  • Lymphocyte Activation / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muramidase / genetics
  • Muramidase / immunology*
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Protein Processing, Post-Translational / immunology*
  • Protein Structure, Tertiary
  • Protein-Tyrosine Kinases / physiology
  • Receptors, Antigen, B-Cell / chemistry*
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / immunology
  • Sequence Deletion
  • Terminator Regions, Genetic

Substances

  • Antigens, CD
  • Autoantigens
  • CD79 Antigens
  • Cd79a protein, mouse
  • Immunoglobulin kappa-Chains
  • Receptors, Antigen, B-Cell
  • Protein-Tyrosine Kinases
  • Muramidase