Cross-linking of B cell antigen receptor-related structure of pre-B cell lines induces tyrosine phosphorylation of p85 and p110 subunits and activation of phosphatidylinositol 3-kinase.
To understand the function of B cell antigen receptor (BCR)-related complex on pre-B cells (pre-BCR, Vpre-B/lambda 5/mu heavy chain/Ig-alpha/Ig-beta), we examined pre-BCR- and BCR-mediated signaling events in human and mouse pre-B (Nalm-6, 697, NFS-5), immature B (IgM+ Daudi, WEHI-231) and mature B (IgM+ IgD+ BALL1) cell lines. Anti-mu cross-linking induced tyrosine phosphorylation of the cytoplasmic proteins in each cell type, but did not induce a detectable Ca2+ mobilization response in pre-B cells. While the pre-B cells expressed Syk protein at levels similar to those found in B cell lines, pre-BCR cross-linkage did not induce phosphorylation of Syk tyrosine residues. Different protein kinase C isozymes were expressed by pre-B (PKC-alpha), immature B (PKC-alpha and -beta) and mature B (PKC-beta) cell lines. Anti-mu cross-linking induced PKC translocation from the cytosolic to the membrane compartment in immature and mature B cells, but did not have this effect in a pre-B cell line. Anti-mu cross-linking induced tyrosine phosphorylation of the p85 and p110 subunits of phosphatidylinositol 3-kinase (P13-kinase) in both pre-B and B cell lines, but the pre-BCR induced P13-kinase activation was Syk independent. Ligation of the pre-BCR complex thus triggers a characteristic signaling pattern in pre-B cells.
Kuwahara
K
K
Department of Immunology, Kumamoto University School of Medicine, Japan.
Kawai
T
T
Mitsuyoshi
S
S
Matsuo
Y
Y
Kikuchi
H
H
Imajoh-Ohmi
S
S
Hashimoto
E
E
Inui
S
S
Cooper
M D
MD
Sakaguchi
N
N
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003432:Cross-Linking Reagents; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase; D014443:Tyrosine / Q000378:metabolism
D003432:Cross-Linking Reagents; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D002118:Calcium