B cell antigen receptor specificity and surface density together determine B-1 versus B-2 cell development

J Exp Med. 1999 Aug 16;190(4):471-7. doi: 10.1084/jem.190.4.471.

Abstract

Mice expressing the immunoglobulin (Ig) heavy (H) chain variable (V) region from a rearranged V(H)12 gene inserted into the IgH locus generate predominantly B-1 cells, whereas expression of two other V(H) region transgenes (V(H)B1-8 and V(H)glD42) leads to the almost exclusive generation of conventional, or B-2, cells. To determine the developmental potential of B cells bearing two distinct B cell antigen receptors (BCRs), one favoring B-1 and the other favoring B-2 cell development, we crossed V(H)12 insertion mice with mice bearing either V(H)B1-8 or V(H)glD42. B cells coexpressing V(H)12 and one of the other V(H) genes are readily detected in the double IgH insertion mice, and are of the B-2 phenotype. In mice coexpressing V(H)12, V(H)B1-8 and a transgenic kappa chain able to pair with both H chains, double H chain-expressing B-2 cells, and B-1 cells that have lost V(H)B1-8 are generated, whereas V(H)B1-8 single producers are undetectable. These data suggest that B-1 but not B-2 cells are selected by antigenic stimuli in whose delivery BCR specificity and surface density are of critical importance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / immunology*
  • Cell Differentiation
  • Gene Targeting
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Variable Region / genetics
  • Mice
  • Mice, Mutant Strains
  • Mutagenesis, Insertional
  • Peritoneal Cavity / cytology
  • Reading Frames
  • Receptors, Antigen, B-Cell / immunology*
  • Spleen / cytology
  • Spleen / immunology

Substances

  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Receptors, Antigen, B-Cell