Developmental differences in B cell receptor-induced signal transduction.
We have compared early signaling events at various stages of B cell differentiation using established mouse cell lines. Clustering of pre-B cell antigen receptor (BCR) or BCR induced the tyrosine phosphorylation of various proteins in all cells, although the phosphorylation pattern differed. In spite of the pre-BCR-induced tyrosine phosphorylation, we could not detect an intracellular Ca(2+) signal in pre-B cells. However, co-clustering of the pre-BCR with CD19 did induce Ca(2+) mobilization. In contrast to the immature and mature B cells, where the B cell linker protein (BLNK) went through inducible tyrosine phosphorylation upon BCR clustering, we observed a constitutive tyrosine phosphorylation of BLNK in pre-B cell lines. Both BLNK and phospholipase C (PLC)gamma were raft associated in unstimulated pre-B cells, and this could not be enhanced by pre-BCR engagement, suggesting a ligand-independent PLC gamma-mediated signaling. Further results indicate that the cell lines representing the immature stage are more sensitive to BCR-, CD19- and type II receptors binding the Fc part of IgG (Fc gamma RIIb)-mediated signals than mature B cells.
Kövesdi
Dorottya
D
Department of Immunology, Loránd Eötvös University, H-1117 Pázmány Péter sétány 1/C, Budapest, Hungary.
Koncz
Gábor
G
Iványi-Nagy
Roland
R
Caspi
Yael
Y
Ishiai
Masamichi
M
Kurosaki
Tomohiro
T
Gergely
János
J
Haimovich
Joseph
J
Sármay
Gabriella
G
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018941:Antigens, CD19 / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D020013:Calcium Signaling; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D021962:Membrane Microdomains / Q000737:chemistry; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011940:Receptor Aggregation; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000032:analysis / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; C113939:B cell linker protein; D002352:Carrier Proteins; C080571:Fc gamma receptor IIB; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D019000:Phosphotyrosine; D019869:Phosphatidylinositol 3-Kinases; D010738:Type C Phospholipases