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Evidence is presented that antigen-sensitive cells require two signals for induction. Normally these two signals are delivered to the cell via the recognition of two determinants on the immunogen: the first the receptor on the antigen-sensitive cell, and the second by the cooperating cell system. The special experimental situation described here depends upon the observation that bacterial lipopolysaccharides (LPS) render immunogenic a variety of haptens. When monovalent haptens (TNP-amino acids) are added to spleen cultures, specific antihapten responses are induced in the presence of LPS. After analyzing competing interpretations of this phenomenon, we propose that the antigenic signal is delivered as the consequence of a conformational change in the receptor upon interacting with antigen, and the second signal is delivered directly via the interaction of LPS with the membrane on the antigen-sensitive cell receiving the antigenic signal, or indirectly via the interaction of LPS with the cooperating cell population. These data imply LPS is not itself a mitogen, but merely completes an inductive stimulus to B cells. The experimental results from these and other studies indicate how these two signals may participate in inductive, suppressive, and paralytic stimuli to antigen-sensitive cells.
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