Cell-Released Non-Specific Stimulators of Antibody-Forming Spleen Cell Populations

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Abstract
Summary: Addition of particulate antigen (e.g., chicken RBC) to a suspension of spleen cells from mice previously immunized with this antigen, will cause the release of a soluble, relatively heat-stable, dialyzable, 260-absorbing material capable of producing a non-specific stimulation of antibody-forming cells in vivo (e.g., of cells forming anti-sheep RBC or anti-E. coli). As in the case of oligodeoxyribonucleotides derived from calf thymus DNA, the non-specific endogenous stimulators (which also appear to be oligodeoxy-ribonucleotides) a) must be administered with antigen, b) enhance the early period of increases in antibody-forming cell populations, and c) are antagonized by kinetin riboside. The stimulators are recoverable from the extracellular environment 60 min after the initiation of in vitro reactions between immune spleen cells and corresponding antigen and can be released from spleen cell populations even when the spleen is harvested as late as 3 weeks after immunization. A corresponding release of non-specific stimulators in vivo by re-exposing animals at time of immunization, with antigen B, to a previously experienced different antigen A, has been noted. The results appear to elucidate the nature of a number of previously observed adjuvant effects and may have a bearing on a number of hitherto unexplained stimulations of immune responses.

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