Mechanism for signaling initiation and termination of B lymphocyte proliferation induced by anti-immunoglobulin.

Several lines of evidence were explored which taken together indicate that both the initiation and the termination signal for activation of rabbit lymphocytes to synthesize DNA in response to anti-rabbit immunoglobulin occurs at an immunoglobulin receptor on the surface membrane of B cells. Thus, the premature removal of anti-rabbit immunoglobulin by simply washing the cells at the 31st hour of a 48-h incubation period caused a 60% decrease in the induction of DNA synthesis. The addition of rabbit immunoglobulin to compete with B cell surface immunoglobulin for the combining sites on anti-rabbit immunoglobulin yielded a markedly diminished activation. Addition of rabbit immunoglobulin even during the latter part of a pulse label period with [3H]-thymidine was sufficient to result in reduced activation. Finally, insoluble anti-rabbit immunoglobulin at the same nominal concentration as soluble anti-rabbit immunoglobulin also was effective in inducing cells to DNA synthesis. However, it is noteworthy that under the incubation conditions used it was not possible to derive a soluble component from insoluble anti-rabbit immunoglobulin which stimulated DNA synthesis. These data have been interpreted to indicate a need for a continuous surface presence of anti-rabbit immunoglobulin to stimulate activation in a process that is not dependent upon internalization of anti-rabbit immunoglobulin.