Deficiency of BLNK hampers PLC-γ2 phosphorylation and Ca2+ influx induced by the pre-B-cell receptor in human pre-B cells

Tomoko Taguchi, Nobutaka Kiyokawa, Hisami Takenouch, Jun Matsui, Wei Ran Tang, Hideki Nakajima, Kyoko Suzuki, Yusuke Shiozawa, Masahiro Saito, Yohko U. Katagiri, Takao Takahashi, Hajime Karasuyama, Yoshinobu Matsuo, Hajime Okita, Junichiro Fujimoto

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

B-cell linker protein (BLNK) is a component of the B-cell receptor (BCR) as well as of the pre-BCR signalling pathway, and BLINK-/- mice have a block in B lymphopoiesis at the pro-B/pre-B cell stage. A recent report described the complete loss or drastic reduction of BLNK expression in approximately 50% of human childhood pre-B acute lymphoblastic leukaemias (ALL), therefore we investigated BLNK expression in human pre-B ALL cell lines. One of the four cell lines tested, HPB-NULL cells, was found to lack BLNK expression, and we used these human pre-B ALL cell lines that express and do not express BLNK to investigate the intracellular signalling events following pre-BCR cross-linking. When pre-BCR was cross-linked with anti-μ heavy-chain antibodies, significant phosphorylation of intracellular molecules, including Syk, Shc, ERK MAP kinase, and AKT, and an activation of Ras were observed without regard to deficiency of BLNK expression, suggesting that BLNK is not required for pre-BCR-mediated activation of MAP kinase and phosphatidyl-inositol 3 (PI3) kinase signalling. By contrast, phospholipase C-γ2 (PLC-γ2) phosphorylation and an increase in intracellular Ca2+ level mediated by pre-BCR cross-linking were observed only in the BLNK-expressing cells, indicating that BLNK is essential for PLC-γ2-induced Ca2+ influx. Human pre-B cell lines expressing and not expressing BLNK should provide an in vitro model for investigation of the role of BLNK in the pre-BCR-mediated signalling mechanism.

Original languageEnglish
Pages (from-to)575-582
Number of pages8
JournalImmunology
Volume112
Issue number4
DOIs
Publication statusPublished - 2004 Aug

Keywords

  • B cells
  • B-cell receptor
  • Signalling/signal transduction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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