Insulin receptor expression in burkitt lymphoma cell lines

The specific binding of insulin to 7 different Burkitt lymphoma cell lines containing chromosomal translocations t(8; 14), t(8;2) and t(8;22) was markedly decreased when compared to binding to lymphoblastoid cells of normal karyotype derived from Burkitt lymphoma patients or the human IM-9 lymphoblastoid line. The number of insulin-binding sites on intact Burkitt cells was decreased by >90% compared to lymphoblastoid cells, with no change in affinity. This decrease in binding was paralleled by reduced amounts of insulin receptor α (Mr 130,000) and β (Mr 95,000) subunits detected by cell-surface-labelling and insulin receptor mRNA transcripts, indicating that transcription of receptor mRNA is decreased in Burkitt cells compared to lymphoblastoid cells and/or that receptor mRNA is less stable. Burkitt cells displayed negligible insulin-stimulated β subunit auto-phosphorylation, which could reflect either their decreased number of receptors or a defect in signal transduction. Structural analysis also revealed that the Burkitt cells had an increase in a precursor form (Mr210,000) of the receptor, suggesting that decreased expression of the receptor may be associated with defective processing. Four Burkitt cell lines with t(8;l4) also had reductions of 45–100% in expression of class-l major histocompatibility (MHC) antigens. The expression of insulin receptors in both Burkitt and lymphoblastoid cells correlated with the expression of class-l MHC antigens. There was also an inverse correlation between the expression of c-myc and both insulin receptors and class-l MHC antigens. As the insulin receptor is absent on resting B cells and is induced after cell activation, the decrease in receptor expression on Burkitt cells may reflect their less activated phenotype compared to lymphoblastoid cells.