The Protein Tyrosine Phosphatase SHP-1 (PTPN6) but Not CD45 (PTPRC) Is Essential for the Ligand-Mediated Regulation of CD22 in BCR-Ligated B Cells

J Immunol. 2021 Jun 1;206(11):2544-2551. doi: 10.4049/jimmunol.2100109. Epub 2021 May 14.


CD22 is an inhibitory B cell coreceptor that regulates B cell development and activation by downregulating BCR signaling through activation of SH2-containing protein tyrosine phosphatase-1 (SHP-1). CD22 recognizes α2,6 sialic acid as a specific ligand and interacts with α2,6 sialic acid-containing membrane molecules, such as CD45, IgM, and CD22, expressed on the same cell. Functional regulation of CD22 by these endogenous ligands enhances BCR ligation-induced signaling and is essential for normal B cell responses to Ags. In this study, we demonstrate that CD45 plays a crucial role in CD22-mediated inhibition of BCR ligation-induced signaling. However, disruption of ligand binding of CD22 enhances CD22 phosphorylation, a process required for CD22-mediated signal inhibition, upon BCR ligation in CD45-/- as well as wild-type mouse B cells but not in mouse B cells expressing a loss-of-function mutant of SHP-1. This result indicates that SHP-1 but not CD45 is required for ligand-mediated regulation of CD22. We further demonstrate that CD22 is a substrate of SHP-1, suggesting that SHP-1 recruited to CD22 dephosphorylates nearby CD22 as well as other substrates. CD22 dephosphorylation by SHP-1 appears to be augmented by homotypic CD22 clustering mediated by recognition of CD22 as a ligand of CD22 because CD22 clustering increases the number of nearby CD22. Our results suggest that CD22 but not CD45 is an endogenous ligand of CD22 that enhances BCR ligation-induced signaling through SHP-1-mediated dephosphorylation of CD22 in CD22 clusters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Cell Line
  • Humans
  • Leukocyte Common Antigens / immunology
  • Ligands
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / immunology*
  • Receptors, Antigen, B-Cell / immunology*
  • Sialic Acid Binding Ig-like Lectin 2 / immunology*


  • CD22 protein, human
  • Ligands
  • Receptors, Antigen, B-Cell
  • Sialic Acid Binding Ig-like Lectin 2
  • Leukocyte Common Antigens
  • PTPN6 protein, human
  • PTPRC protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6