THE SKW-6.4 LINE OF HUMAN B-LYMPHOCYTES SPECIFICALLY BINDS AND RESPONDS TO VASOACTIVE-INTESTINAL-PEPTIDE

Vasoactive intestinal peptide (VIP1-28) is a neuromediator recognized by high-affinity receptors on human lymphocytes, which inhibits T-cell proliferation and cytokine secretion, and suppresses immunoglobulin p roduction by mitogen-stimulated mixed mononuclear leucocytes. The dire ct interactions of VIP1-28 with B cells were studied in the SKW 6.4 li ne of EBV-transformed human B cells, that express a mean (+/- SD) of 6 116 +/- 969 receptors for [I-125]VIP1-28 with a mean K(d) of 59 nm, th at decreases to 12 nm after exposure to phorbol 12-myristate 13-acetat e (PMA). The secretion of IgM by SKW 6.4 B cells stimulated optimally with 100 ng/ml of PMA, but not unstimulated secretion of IgM, was supp ressed significantly by 10(-12) M to 10(-9) M VIP1-28 and up to a mean maximum (+/- SD) of 40 +/- 2% by 10(-10) M VIP1-28. VIP1-28 elicited concomitant increases in intracellular cyclic AMP up to a mean maximum of 163% at 10(-10) M VIP1-28. The requirement for specific signal tra nsduction by the occupied VIP receptors to inhibit IgM secretion was d emonstrated by the lack of effect of VIP4-28 on both cyclic AMP concen tration and IgM secretion, despite the equal affinity of binding of VI P4-28 and VIP1-28. The effects of VIP on immunoglobulin secretion by s timulated mixed mononuclear leucocytes thus may be due in part to a di rect action on B cells.