Antibody Formation: Initiation in "Nonresponder" Mice by Macrophage Synthetic Polypeptide RNA

Abstract

The RNA extracted from normal peritoneal macrophages exposed to a linear, random synthetic polypeptide, Glu(60)Ala(30)Tyr(10), initiated an immune response in C57B1/6J mice, although this strain responds very poorly to the antigen itself. From 10 to 150 micrograms of RNA obtained from mouse, rat, or rabbit macrophages was injected intraperitoneally into recipient mice, and specific antibody was detectable by passive hemagglutination 3 to 4 weeks later. Treatment of the RNA with ribonuclease destroyed its ability to initiate a specific immune response. The RNA contained by weight 0.02 percent of the (specific) antigen. The RNA obtained from cells incubated with a second polypeptide, Glu(36)Lys(24)Ala(40), initiated a response specific for this polymer. This RNA even when incubated in vitro with Glu(60)Ala(30)Tyr(10) failed to initiate antibody formation specific for Glu(60)Ala(30)Tyr(10).

Cellular Differentiation of the Immune System of Mice

“…Perhaps cells with intermediate properties of differentiation and maturation can be found in marrow-thymus mixtures (16,17) or in fetal tissues. Differentiation may have occurred either in all cell components of an antigen-sensitive unit (15)(16)(17) or only in a single cell type such as macrophages processing antigen, thymocytes, or cells synthesizing immunogiobulins. Results of preliminary experiments suggest that antigen-sensitive units resulting from bone marrow-thymocyte mixtures are also unipotent with respect to anti-SRBC immunocyte production.…”

Tolerance-Mediated Inheritance of Immune Responsiveness

“…In these instances, it seems clear that tolerance-mediation, as proposed in the 'steering mechanism' [7], cannot be responsible for themechanism of this inheritance and other genetic pathways have to be sought. This type of control may concern a macrophage-mediated processing step [31] in some instances, and in other instances may depend on the genetic control of the threshold between the quantities of antigen which induce tolerance and the quantities which induce antibody formation [33,24] …”

Production of cytotoxic antibody to a benz(a)pyrene-induced sarcoma in mice receiving xenogeneic antitumor immune RNA

“…Normal nonimmune lymphoid cells incubated in such RNA preparations in vitro were subsequently shown to mediate a variety of cellular and humoral immune responses both in vivo and in vitro. These include the production of antibody specific for the antigen used to sensitize the RNA-donor lymphoid cells [I, 5,6,8,15,16,32,34], induction of zones of localized hemolysis in gels [9,17,18], and inhibition of macrophage migration in capillary tubes upon exposure to specific antigen [23,40,41]. In 1962, Mannick and Egdahl reported the successful transfer of immune responses to normal transplantation antigens with allogeneic immune RNA (I-RNA) extracted from the lymphoid organs of specifically immunized rabbits [29,30].…”