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Deficiency of BLNK hampers PLC‐γ2 phosphorylation and Ca 2+ influx induced by the pre‐B‐cell receptor in human pre‐B cells
Author(s) -
Taguchi Tomoko,
Kiyokawa Nobutaka,
Takenouch Hisami,
Matsui Jun,
Tang WeiRan,
Nakajima Hideki,
Suzuki Kyoko,
Shiozawa Yusuke,
Saito Masahiro,
Katagiri Yohko U.,
Takahashi Takao,
Karasuyama Hajime,
Matsuo Yoshinobu,
Okita Hajime,
Fujimoto Junichiro
Publication year - 2004
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2004.01918.x
Subject(s) - biology , microbiology and biotechnology , b cell receptor , phosphorylation , b cell , breakpoint cluster region , intracellular , kinase , receptor , antibody , immunology , genetics
Summary B‐cell linker protein (BLNK) is a component of the B‐cell receptor (BCR) as well as of the pre‐BCR signalling pathway, and BLNK –/– 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 Ca 2+ level mediated by pre‐BCR cross‐linking were observed only in the BLNK‐expressing cells, indicating that BLNK is essential for PLC‐γ2‐induced Ca 2+ 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.