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

Amin Alborzian Deh Sheikh, Chizuru Akatsu, Hajjaj H.M. Abdu-Allah, Yuki Suganuma, Akihiro Imamura, Hiromune Ando, Hiromu Takematsu, Hideharu Ishida, Takeshi Tsubata

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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 a2,6 sialic acid as a specific ligand and interacts with a2,6 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 ligationinduced signaling. However, disruption of ligand binding of CD22 enhances CD22 phosphorylation, a process required for CD22- mediated signal inhibition, upon BCR ligation in CD452/2 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.

Original languageEnglish
Pages (from-to)2544-2551
Number of pages8
JournalJournal of Immunology
Volume206
Issue number11
DOIs
Publication statusPublished - 01-06-2021

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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