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 production by mitogen-stimulated mixed mononuclear leucocytes. The direct interactions of VIP1-28 with B cells were studied in the SKW 6.4 line of EBV-transformed human B cells, that express a mean (+/- SD) of 6116 +/- 969 receptors for [125I]VIP1-28 with a mean Kd of 59 nM, that decreases to 12 nM after exposure to phorbol 12-myristate 13-acetate (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 suppressed 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 transduction by the occupied VIP receptors to inhibit IgM secretion was demonstrated by the lack of effect of VIP4-28 on both cyclic AMP concentration and IgM secretion, despite the equal affinity of binding of VIP4-28 and VIP1-28. The effects of VIP on immunoglobulin secretion by stimulated mixed mononuclear leucocytes thus may be due in part to a direct action on B cells.
Department of Medicine, University of California Medical Center, San Francisco 94143-0724.
P P
PP
Cheng
S P
SP
Sreedharan
J L
JL
Kishiyama
E J
EJ
Goetzl
D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007075:Immunoglobulin M / Q000096:biosynthesis; D066298:In Vitro Techniques; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology
D007075:Immunoglobulin M; D014660:Vasoactive Intestinal Peptide; D013755:Tetradecanoylphorbol Acetate