The lectin Jacalin induces human B‐lymphocyte apoptosis through glycosylation‐dependent interaction with CD45

Abstract

SummaryIt 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 a-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 calciumcalpain 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.

Skin mucus proteins of lumpsucker (Cyclopterus lumpus)

“…The lectin like domain in natterin is homologous to Jacalin domain identified in jack fruit. Little work has been done on natterin in fish but jacalin, the plant homologue, is reported to be involved in activation of human T- lymphocytes [24] and apoptosis of B-lymphocytes [25] suggesting a role in the immune system of fish. In mucus the lectin domain could give direct interaction with pathogens and the pore forming toxin domain could potentially result in lysis ( Fig.…”

Astragalus membranaceus lectin (AML) induces caspase‐dependent apoptosis in human leukemia cells

“…Some plant lectins, such as those of mistletoe, which also bind specifically through lactose or galactose, bring about caspase‐dependent apoptosis through mitochondria and/or death receptors of human tumour cells (12,13,36) and apoptosis of K562 cells caused by a D‐galactose lectin (CvL) via a caspase‐independent mechanism, has been reported (30). A Galβ1‐3Gal‐NAc‐binding lectin (Jacalin) from jackfruit seeds inhibited CD45 tyrosine phosphatase activity of human B lymphocytes resulting in apoptosis (37). Thus, molecular mechanisms of lectin‐induced apoptosis of tumour cells seems to be complex and cannot be judged simply by carbohydrate‐binding property of lectins.…”

Involvement of tyrosine phosphatase CD45 in apoptosis

“…Jacalin induces B cell apoptosis, resulting in calcium mobilization and calpain activation, suggesting that the calcium-calpain pathway may mediate the Jacalininduced apoptosis. The apoptosis is blocked by a specific CD45 PTPase inhibitor, indicating that Jacalin induces B cell apoptosis through CD45 triggering [85]. In T cells, this lectin bound to CD45 caused an increase in T-cell activation in response to T-cell receptor ligation and CD28 co-stimulation [86].…”

“…Recently, Ma et al [85] reported that the lectin Jacalin induces apoptosis in B cells through glycosylation-dependent interaction with CD45. Jacalin is a Thomsen-Friedenreich antigen-specific lectin from jackfruit seeds that could be a major receptor for CD45 isoforms on B lymphocytes.…”