B cell Ag receptor mediates different types of signals in the protein kinase activity between immature B cell and mature B cell.
Ig receptor (IgR) on the surface of B cells mediates the Ag-specific stimulatory signal for B cell proliferation and differentiation. In immature B cells, the stimulatory signal causes an inhibitory effect which is believed to be a key phenomenon in B cell tolerance or B cell anergy. Here, we studied the molecular mechanism of the inhibitory response of the IgR-mediated signal transduction that results in the programmed cell death of immature B cells. To analyze the downstream molecules of the IgR-mediated signal transduction, we prepared a mAb against a 160-kDa membrane protein (p160) that can coprecipitate the kinase molecule(s) acting on serine, threonine, and tyrosine residues. Anti-IgR stimulation induces the increase of the kinase activity coprecipitated with the p160 protein in mature B cell BAL17 and normal adult spleen B cells. This result suggest that the p160-associated kinase activity is one of the downstream events of the IgR-mediated signal transduction cascade. Interestingly, immature B cell lymphoma WEHI-231 and the neonatal spleen B cells showed the adverse reaction of the p160-associated kinase which results in the transient loss of the kinase activity. Moreover, the transient decrease of the p160-associated kinase was caused by the tyrosine phosphatase activity induced by the stimulation of IgR in WEHI-231. The results suggest that this molecular difference in the downstream events of the IgR-mediated signal transduction between immature B cells and mature B cells already begins at the transmembrane level in the IgR-mediated signal transduction pathway.
Igarashi
H
H
Department of Immunology, School of Life Science, Faculty of Medicine, Tottori University, Yonago, Japan.
Kuwahara
K
K
Nomura
J
J
Matsuda
A
A
Kikuchi
K
K
Inui
S
S
Sakaguchi
N
N
D000818:Animals; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D008970:Molecular Weight; D011233:Precipitin Tests; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D013154:Spleen / Q000166:cytology
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D008565:Membrane Proteins; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases; D002118:Calcium