Studies on the adjuvant action of beryllium. IV. The preparation of beryllium containing macromolecules that induce immunoblast responses in vivo.

Solutions of BeSO4 were added to soluble macromolecules and the mixtures brought to neutrality. Under appropriate conditions much of the beryllium did not precipitate out as insoluble hydroxides but became attached to naturally occurring sulphated proteoglycans and polysaccharides (e.g. heparin, chondroitin sulphate, fucoidan, etc.) and to synthetic, sulphonated aromatic dyestuffs (e.g. trypan, Evans and Coomassie blues, Suramin, etc.). At physiological conditions of pH and ionic strength, these addition compounds were relatively stable and did not dissociate during dialysis. When such materials were injected s.c. into sheep (in doses containing about 50 micrograms Be), rapid lymphoproliferative responses took place in the regional nodes so that immunoblasts appeared in the efferent lymph in numbers that exceeded those provoked by powerful conventional antigenic stimuli. Significant amounts of the injected materials passed through the nodes and, in intact animals, became systematized. A method was devised for attaching beryllium to particulate carriers, such as lymphocytes or red cells that had been fixed with glutaraldehyde. The injection of suspensions of such materials also provoked vigorous immunoblastic responses, but the particulate materials did not pass beyond the regional node. In the doses usually used, none of these materials was grossly toxic and they may be suitable for consideration for development into a new type of immunostimulator cum adjuvant.