Bruton's tyrosine kinase and phospholipase C gamma 2 mediate chemokine-controlled B cell migration and homing

David J. J. de Gorter; Esther A. Beuling; Rogier Kersseboom; Sabine Middendorp; Janine M. van Gils; Rudolf W. Hendriks; Steven T. Pals; Marcel Spaargaren

doi:10.1016/j.immuni.2006.11.012

Bruton's tyrosine kinase and phospholipase C gamma 2 mediate chemokine-controlled B cell migration and homing

David J. J. de Gorter, Esther A. Beuling, Rogier Kersseboom, Sabine Middendorp, Janine M. van Gils, Rudolf W. Hendriks, Steven T. Pals, Marcel Spaargaren^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Control of integrin-mediated adhesion and migration by chemokines plays a critical role in B cell development, differentiation, and function; however, the underlying signaling mechanisms are poorly defined. Here we show that the chemokine SDF-1 induced activation of Bruton's tyrosine kinase (Btk) and that integrin-mediated adhesion and migration in response to SDF-1 or CXCL13, as well as in vivo homing to lymphoid organs, was impaired in Btk-deficient (pre-)B cells. Furthermore, SDF-1 induced tyrosine phosphorylation of Phospholipase C gamma 2 (PLC gamma 2), which, unlike activation of the migration regulatory GTPases Rac or Rap1, was mediated by Btk. PLC gamma 2-deficient B cells also exhibited impaired SDF-1-controlled migration. These results reveal that Btk and PLC gamma 2 mediate chemokine-controlled migration, thereby providing insights into the control of B cell homeostasis, trafficking, and function, as well as into the pathogenesis of the immunodeficiency disease X-linked agammaglobulinemia (XLA).

Original language	English
Pages (from-to)	93-104
Number of pages	12
Journal	Immunity
Volume	26
Issue number	1
DOIs	https://doi.org/10.1016/j.immuni.2006.11.012
Publication status	Published - Jan 2007
Externally published	Yes

Keywords

HEMATOPOIETIC PROGENITOR CELLS
FOCAL ADHESION PROTEINS
TEC FAMILY KINASES
BONE-MARROW
PHOSPHOINOSITIDE 3-KINASES
INTEGRIN ACTIVATION
ANTIGEN RECEPTOR
LYMPHOCYTE CHEMOTAXIS
SIGNAL-TRANSDUCTION
ALPHA-4 INTEGRINS

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10.1016/j.immuni.2006.11.012

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@article{9b312580a4ee4c40a142651446e0d922,

title = "Bruton's tyrosine kinase and phospholipase C gamma 2 mediate chemokine-controlled B cell migration and homing",

abstract = "Control of integrin-mediated adhesion and migration by chemokines plays a critical role in B cell development, differentiation, and function; however, the underlying signaling mechanisms are poorly defined. Here we show that the chemokine SDF-1 induced activation of Bruton's tyrosine kinase (Btk) and that integrin-mediated adhesion and migration in response to SDF-1 or CXCL13, as well as in vivo homing to lymphoid organs, was impaired in Btk-deficient (pre-)B cells. Furthermore, SDF-1 induced tyrosine phosphorylation of Phospholipase C gamma 2 (PLC gamma 2), which, unlike activation of the migration regulatory GTPases Rac or Rap1, was mediated by Btk. PLC gamma 2-deficient B cells also exhibited impaired SDF-1-controlled migration. These results reveal that Btk and PLC gamma 2 mediate chemokine-controlled migration, thereby providing insights into the control of B cell homeostasis, trafficking, and function, as well as into the pathogenesis of the immunodeficiency disease X-linked agammaglobulinemia (XLA).",

keywords = "HEMATOPOIETIC PROGENITOR CELLS, FOCAL ADHESION PROTEINS, TEC FAMILY KINASES, BONE-MARROW, PHOSPHOINOSITIDE 3-KINASES, INTEGRIN ACTIVATION, ANTIGEN RECEPTOR, LYMPHOCYTE CHEMOTAXIS, SIGNAL-TRANSDUCTION, ALPHA-4 INTEGRINS",

author = "{de Gorter}, {David J. J.} and Beuling, {Esther A.} and Rogier Kersseboom and Sabine Middendorp and {van Gils}, {Janine M.} and Hendriks, {Rudolf W.} and Pals, {Steven T.} and Marcel Spaargaren",

year = "2007",

month = jan,

doi = "10.1016/j.immuni.2006.11.012",

language = "English",

volume = "26",

pages = "93--104",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "1",

}

TY - JOUR

T1 - Bruton's tyrosine kinase and phospholipase C gamma 2 mediate chemokine-controlled B cell migration and homing

AU - de Gorter, David J. J.

AU - Beuling, Esther A.

AU - Kersseboom, Rogier

AU - Middendorp, Sabine

AU - van Gils, Janine M.

AU - Hendriks, Rudolf W.

AU - Pals, Steven T.

AU - Spaargaren, Marcel

PY - 2007/1

Y1 - 2007/1

N2 - Control of integrin-mediated adhesion and migration by chemokines plays a critical role in B cell development, differentiation, and function; however, the underlying signaling mechanisms are poorly defined. Here we show that the chemokine SDF-1 induced activation of Bruton's tyrosine kinase (Btk) and that integrin-mediated adhesion and migration in response to SDF-1 or CXCL13, as well as in vivo homing to lymphoid organs, was impaired in Btk-deficient (pre-)B cells. Furthermore, SDF-1 induced tyrosine phosphorylation of Phospholipase C gamma 2 (PLC gamma 2), which, unlike activation of the migration regulatory GTPases Rac or Rap1, was mediated by Btk. PLC gamma 2-deficient B cells also exhibited impaired SDF-1-controlled migration. These results reveal that Btk and PLC gamma 2 mediate chemokine-controlled migration, thereby providing insights into the control of B cell homeostasis, trafficking, and function, as well as into the pathogenesis of the immunodeficiency disease X-linked agammaglobulinemia (XLA).

AB - Control of integrin-mediated adhesion and migration by chemokines plays a critical role in B cell development, differentiation, and function; however, the underlying signaling mechanisms are poorly defined. Here we show that the chemokine SDF-1 induced activation of Bruton's tyrosine kinase (Btk) and that integrin-mediated adhesion and migration in response to SDF-1 or CXCL13, as well as in vivo homing to lymphoid organs, was impaired in Btk-deficient (pre-)B cells. Furthermore, SDF-1 induced tyrosine phosphorylation of Phospholipase C gamma 2 (PLC gamma 2), which, unlike activation of the migration regulatory GTPases Rac or Rap1, was mediated by Btk. PLC gamma 2-deficient B cells also exhibited impaired SDF-1-controlled migration. These results reveal that Btk and PLC gamma 2 mediate chemokine-controlled migration, thereby providing insights into the control of B cell homeostasis, trafficking, and function, as well as into the pathogenesis of the immunodeficiency disease X-linked agammaglobulinemia (XLA).

KW - HEMATOPOIETIC PROGENITOR CELLS

KW - FOCAL ADHESION PROTEINS

KW - TEC FAMILY KINASES

KW - BONE-MARROW

KW - PHOSPHOINOSITIDE 3-KINASES

KW - INTEGRIN ACTIVATION

KW - ANTIGEN RECEPTOR

KW - LYMPHOCYTE CHEMOTAXIS

KW - SIGNAL-TRANSDUCTION

KW - ALPHA-4 INTEGRINS

U2 - 10.1016/j.immuni.2006.11.012

DO - 10.1016/j.immuni.2006.11.012

M3 - Article

C2 - 17239630

SN - 1074-7613

VL - 26

SP - 93

EP - 104

JO - Immunity

JF - Immunity

IS - 1

ER -

Bruton's tyrosine kinase and phospholipase C gamma 2 mediate chemokine-controlled B cell migration and homing

Abstract

Keywords

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