Mouse spleen cells were incubated with anti-Ig antibodies for 1 h, washed, exposed to LPS for 1 h, washed, and their DNA synthetic responses assayed 2 days later. It was shown that the 1-h incubation with anti-Ig antibodies produced a profound, internal, and long lasting state of inactivation in the B cells. Experiments with anti-Ig fragments and other ligands showed that the inactivation occurred optimally when both surface Ig molecules and Fc receptors were bound simultaneously. The role of the classical capping and clearing cycle was also investigated. It was shown that capping and clearing were neither necessary nor sufficient for the inactivation to occur, and that the signals, but only secondarily the ligands themselves, were transmitted across the membrane. Capping and clearing were viewed as a natural regulatory mechanism by which the B cell attempts to clear its membrane of perturbations and signals from the exterior.

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