Btk and phospholipase Cγ2 can function independently during B cell development

Kristina E. Halcomb, Cristina M. Contreras, Rochelle M. Hinman, Terry G. Coursey, Heather L. Wright, Anne B. Satterthwaite

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The pre-BCR and the BCR regulate B cell development via a signalosome nucleated by the adaptor protein B cell linker protein (BLNK). Formation of this complex facilitates activation of phospholipase C (PLC) γ2 by Bruton's tyrosine kinase (Btk). To determine whether Btk and PLCγ2 also have separate functions, we generated Btk-/-PLCγ2-/- mice. They demonstrated a block in development at the pre-B stage and increased pre-BCR surface expression. This phenotype was more severe than that of Btk%-/- or PLCγ2-/- mice. Although both Btk and PLCγ2 were required for proliferation of splenic B cells in response to BCR cross-linking, they contributed differently to anti-IgM-induced phosphorylation of ERK. Btk-/- and PLCγ2-/- mice each had a reduced frequency of Igλ-expressing B cells and impaired migration of pre-B cells towards stromal cell-derived factor 1. However, the increase in pre-B cell malignancy that occurs in BLNK-/- mice in the absence of Btk was not observed in the absence of PLCγ2. Thus, Btk and PLCγ2 act both in concert and independently throughout B cell development.

Original languageEnglish (US)
Pages (from-to)1033-1042
Number of pages10
JournalEuropean Journal of Immunology
Volume37
Issue number4
DOIs
StatePublished - Apr 2007

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Phospholipases
B-Lymphocytes
B-Lymphoid Precursor Cells
Chemokine CXCL12
Agammaglobulinaemia tyrosine kinase
Type C Phospholipases
Cell Movement
Phosphorylation
Phenotype

Keywords

  • B cell linker protein
  • ERK
  • Lymphoma
  • Pre-B cell
  • Stromal cell-derived factor 1

ASJC Scopus subject areas

  • Immunology

Cite this

Btk and phospholipase Cγ2 can function independently during B cell development. / Halcomb, Kristina E.; Contreras, Cristina M.; Hinman, Rochelle M.; Coursey, Terry G.; Wright, Heather L.; Satterthwaite, Anne B.

In: European Journal of Immunology, Vol. 37, No. 4, 04.2007, p. 1033-1042.

Research output: Contribution to journalArticle

Halcomb, Kristina E. ; Contreras, Cristina M. ; Hinman, Rochelle M. ; Coursey, Terry G. ; Wright, Heather L. ; Satterthwaite, Anne B. / Btk and phospholipase Cγ2 can function independently during B cell development. In: European Journal of Immunology. 2007 ; Vol. 37, No. 4. pp. 1033-1042.
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