Suppression of human T and B lymphocyte activation by Agaricus bisporus lectin. I. Suggestive evidence for a surface "suppressor" receptor in human lymphocytes.

Abstract

Agaricus bisporus lectin (ABL), a Phytohemagglutinin prepared from the golden white mushroom, markedly suppresses DNA synthesis and immunoglobulin production in human T and B lymphocytes, respectively. ABL produces dose-related inhibition of DNA synthesis in both unseparated peripheral blood lymphocytes and highly purified T cells activated with several polyclonal stimulants, including the mitogenic lectins, PHA or Con A; the recall antigen, tetanus toxoid; or the calcium ionophore, A23187. Similarly, ABL inhibits human B cell metabolism as indicated by decreased DNA synthesis in highly purified B cells stimulated with the Epstein-Barr virus and markedly diminished rates of pokeweed mitogen-activated immunoglobulin production in unseparated peripheral blood lymphocytes. ABL inhibition of DNA synthesis and immunoglobulin production is not associated with cell death, and the normal DNA synthetic response is completely restored after delayed elution of membrane-associated ABL. In accord with the known binding specificity of this lectin for d-galactose and N-acetyl-d-galactosamine, these simple sugars as well as d-lactose and L-rhamnose block ABL inhibition of DNA synthesis and immunoglobulin production. Studies of radiolabeled ABL cell surface binding revealed 15.7 million receptors per human lymphocyte with an average ABL-receptor binding constant of 1.3 × 105 L/M. Furthermore, binding of ABL to these receptors is markedly reduced in cells previously exposed to low concentrations of other defined suppressors of lymphocyte metabolism including the exogenous lectin wheat germ agglutinin and endogenous lectins present in a Con A-stimulated soluble immune suppressor supernatant (SISS). Each of these suppressors also interacts with specific surface carbohydrate residues. These data provide suggestive evidence for the presence of a group of specific glycoprotein or glycolipid surface receptors, which, after activation by any of these suppressive ligands, generates a negative intracellular signal that culminates in suppression of human T and B cell metabolism.