Ikaros has a crucial role in regulation of B cell receptor signaling.
The transcription factor Ikaros, a key regulator of hematopoiesis, has an essential role in lymphocyte development. In mice, fetal lymphoid differentiation is blocked in the absence of Ikaros, and whereas T cells develop postnatally, B cells are totally absent. The significance of Ikaros in the B cell development is evident, but how Ikaros regulates B cell function has neither been established nor previously been studied with B cells that lack Ikaros expression. Here we show that disruption of Ikaros in the chicken B cell line DT40 induces a B cell receptor (BCR) signaling defect with reduced phospholipase Cgamma2 phosphorylation and impaired intracellular calcium mobilization, which is restored by Ikaros reintroduction. Furthermore, we show that lack of Ikaros induces hyperphosphorylation of Casitas B lymphoma protein subsequent to BCR activation. These results indicate that the absolute need of Ikaros for development, cell fate decisions and maintenance of B cells is due to the enhancement of BCR signaling.
Nera
Kalle-Pekka
KP
Turku Graduate School of Biomedical Sciences, University of Turku, Turku, Finland. kalle-pekka.nera@utu.fi
Alinikula
Jukka
J
Terho
Perttu
P
Narvi
Elli
E
Törnquist
Kid
K
Kurosaki
Tomohiro
T
Buerstedde
Jean-Marie
JM
Lassila
Olli
O
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002645:Chickens / Q000276:immunology*; D051740:Ikaros Transcription Factor / Q000172:deficiency / Q000276:immunology*; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology*; D050722:Oncogene Protein v-cbl / Q000276:immunology; D051966:Phospholipase C gamma / Q000276:immunology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D050722:Oncogene Protein v-cbl; D011947:Receptors, Antigen, B-Cell; D051740:Ikaros Transcription Factor; D051966:Phospholipase C gamma