Modulation of B lymphocyte antigen receptor signal transduction by a CD19/CD22 regulatory loop

Immunity. 1999 Aug;11(2):191-200. doi: 10.1016/s1074-7613(00)80094-1.

Abstract

CD19 and CD22 are B lymphocyte cell-surface molecules that positively and negatively regulate antigen receptor signal transduction, respectively. Biochemical studies with B cells from CD19-deficient and CD22-deficient mice indicated that these two regulatory molecules influenced each other's functions: CD22 expression negatively regulated CD19 tyrosine phosphorylation, while optimal CD22 function was dependent on CD19 expression. Functional CD19 and CD22 interactions were also assessed in vivo by generating CD19/CD22 double-deficient mice. Remarkably, the CD19 mutation was dominant to the CD22 mutation in most instances. B lymphocytes from CD19/CD22-deficient and CD19-deficient mice were functionally equivalent despite the negative influence normally provided by CD22 expression. These data collectively suggest that CD19 activates the CD22/SHP1 inhibitory pathway that then acts primarily on CD19.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibody Formation
  • Antigens, CD / physiology*
  • Antigens, CD19 / physiology*
  • Antigens, Differentiation, B-Lymphocyte / physiology*
  • Calcium / metabolism
  • Cell Adhesion Molecules*
  • Immunoglobulin M / analysis
  • Intracellular Signaling Peptides and Proteins
  • Lectins*
  • Mice
  • Phosphorylation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / metabolism
  • Receptors, Antigen, B-Cell / analysis
  • Receptors, Antigen, B-Cell / physiology*
  • Sialic Acid Binding Ig-like Lectin 2
  • Signal Transduction*
  • Tyrosine / metabolism
  • src-Family Kinases / metabolism

Substances

  • Antigens, CD
  • Antigens, CD19
  • Antigens, Differentiation, B-Lymphocyte
  • Cd22 protein, mouse
  • Cell Adhesion Molecules
  • Immunoglobulin M
  • Intracellular Signaling Peptides and Proteins
  • Lectins
  • Receptors, Antigen, B-Cell
  • Sialic Acid Binding Ig-like Lectin 2
  • Tyrosine
  • lyn protein-tyrosine kinase
  • src-Family Kinases
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • Ptpn11 protein, mouse
  • Ptpn6 protein, mouse
  • Calcium