SPECTRUM AND MODE OF ACTION OF POLY A:U IN THE STIMULATION OF IMMUNE RESPONSES

It is now almost 20 years since we recognized that nucleic acids, apart from their specific informative properties based on nucleotide sequences, also can exert important regulating effects that are basically independent of nucleotide sequences. First in studies with bacteria, and later in studies with mammalian cells (compare Braun and Firshein, 1967), we as well as a few others (for example, Johnson, 1968) observed that oligo- and polynucleotides, in contrast to ineffective mononucleotides, can alter the rate of a number of biosynthetic events including rates of cell multiplication. When synthetic polynucleotides became available we tested their effects in a system that had proved susceptible to stimulation by natural oligo- and polynucleotides, namely antibody formation. At first, using single-stranded polynucleotides, such as poly A, poly U, poly C., and poly G, we found no effects. We were about to discard these homopolymers as inactive, when we made a final trial to determine the possible effectiveness of a mixture of these homo-polymers and discovered, in tests on antibody formation to sheep red blood cells (sRBC) in mice, a pronounced stimulation (Braun and Nakano, 1967). The rest is now history, documented by much of what is being reviewed at this Symposium: Complementary homopolymers, such as double-stranded poly A : U, poly C : G, or poly I : C., influence the behavior of cells involved in immune responses.