The lectin Jacalin induces human B-lymphocyte apoptosis through glycosylation-dependent interaction with CD45.
It has been well established that CD45 is a key receptor-type protein tyrosine phosphatase (PTPase) regulating Src-family protein tyrosine kinase (Src-PTK) in T and B lymphocytes. However, precisely how CD45 exerts its effect in these lymphocytes remains controversial. We recently reported that Jacalin, an alpha-O-glycoside of the disaccharide Thomsen-Friedenreich antigen-specific lectin from jackfruit seeds, caused marked T-cell activation in response to T-cell receptor ligation and CD28 costimulation by binding to CD45. On extending the reported research, we found that CD45 and isoforms are major Jacalin receptors on B lymphocytes, and that the glycosylation of CD45 is involved in the interaction of Jacalin with the PTPase. In contrast to Jacalin-stimulated T-cell activation, we found that Jacalin induced human B-lymphocyte apoptosis, resulting in calcium mobilization and calpain activation, suggesting that the calcium-calpain pathway may mediate the Jacalin-induced apoptosis. Importantly, the apoptosis was effectively blocked by a specific CD45 PTPase inhibitor, indicating that Jacalin induces human B-lymphocyte apoptosis through CD45 triggering. Furthermore, we found that Jacalin significantly increased the C-terminal inhibitory tyrosine (Tyr507) phosphorylation of Src-PTK Lyn, one of the major substrates of CD45 PTPase, and this effect was also observed on incubation of B lymphocytes with the specific CD45 PTPase inhibitor, suggesting that Jacalin stimulation results in increasing C-terminal tyrosine phosphorylation of the kinase through inhibition of CD45 tyrosine phosphatase activity in human B lymphocytes. Therefore, the down-modulation of Lyn kinase may play a role in the regulation of B-lymphocyte viability.
Ma
Bruce Yong
BY
Research Center for Glycobiotechnology, Ritsumeikan University, Shiga, Japan. byma@fc.ritsumei.ac.jp
Yoshida
Kaori
K
Baba
Makoto
M
Nonaka
Motohiro
M
Matsumoto
Shogo
S
Kawasaki
Nobuko
N
Asano
Shinji
S
Kawasaki
Toshisuke
T
D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D002241:Carbohydrates / Q000276:immunology; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D006031:Glycosylation; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D010766:Phosphorylation / Q000276:immunology; D037121:Plant Lectins / Q000276:immunology*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011975:Receptors, Mitogen / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000276:immunology
D002241:Carbohydrates; D037121:Plant Lectins; D011975:Receptors, Mitogen; C043696:jacalin; C519907:jacalin receptor, human; D014443:Tyrosine; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases; D002154:Calpain; D002118:Calcium