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 language | English (US) |
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Pages (from-to) | 1033-1042 |
Number of pages | 10 |
Journal | European Journal of Immunology |
Volume | 37 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2007 |
Keywords
- B cell linker protein
- ERK
- Lymphoma
- Pre-B cell
- Stromal cell-derived factor 1
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology