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) |
|---|---|
| Pages (from-to) | 1033-1042 |
| Number of pages | 10 |
| Journal | European Journal of Immunology |
| Volume | 37 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2007 |
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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 journal › Article
}
TY - JOUR
T1 - Btk and phospholipase Cγ2 can function independently during B cell development
AU - Halcomb, Kristina E.
AU - Contreras, Cristina M.
AU - Hinman, Rochelle M.
AU - Coursey, Terry G.
AU - Wright, Heather L.
AU - Satterthwaite, Anne B.
PY - 2007/4
Y1 - 2007/4
N2 - 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.
AB - 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.
KW - B cell linker protein
KW - ERK
KW - Lymphoma
KW - Pre-B cell
KW - Stromal cell-derived factor 1
UR - http://www.scopus.com/inward/record.url?scp=34249670327&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249670327&partnerID=8YFLogxK
U2 - 10.1002/eji.200636451
DO - 10.1002/eji.200636451
M3 - Article
C2 - 17372989
AN - SCOPUS:34249670327
VL - 37
SP - 1033
EP - 1042
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 4
ER -