Btk and phospholipase C gamma 2 can function independently during B cell development.
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) gamma2 by Bruton's tyrosine kinase (Btk). To determine whether Btk and PLCgamma2 also have separate functions, we generated Btk(-/-)PLCgamma2(-/-) 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 PLCgamma2(-/-) mice. Although both Btk and PLCgamma2 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 PLCgamma2(-/-) mice each had a reduced frequency of Iglambda-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 PLCgamma2. Thus, Btk and PLCgamma2 act both in concert and independently throughout B cell development.
Halcomb
Kristina E
KE
Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390-8884, USA.
Contreras
Cristina M
CM
Hinman
Rochelle M
RM
Coursey
Terry G
TG
Wright
Heather L
HL
Satterthwaite
Anne B
AB
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000201:enzymology*; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051966:Phospholipase C gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D007527:Isoenzymes; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse; D051966:Phospholipase C gamma