The membrane potential of lymphocytes changes only in response to specific stimulation

We have recently shown [Kiefer H, Blume AJ & Kaback HR (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 2200-2204] that depolarization of the lymphocyte membrane constitutes an early event in mitogenic stimulation. We now present evidence that these early changes in membrane potential occur only as a consequence of specific binding of lipopolysaccharide (LPS) or concanavalin A (Con A) to cells displaying the correct functional receptors. Spleen cells from LPS low-responder mice (C3H/HeJ) show no depolarization with LPS but only with Con A, while those of the LPS high-responder (C3H/Tif Bom) depolarize upon addition of LPS and Con A. Moreover, in T cells, depleted of I-A-bearing cells, the depolarization produced by a specific stimulus is only reversed by the addition of growth factors, thus indicating that mitogenic activation of lymphocytes is at least a two-signal mechanism. These early events could more recently be correlated with changes in intracellular pH [Gerson DF, Kiefer H & Eufe W (1982) Science 216, 1009-1010; Gerson DF & Kiefer H (1982) J. Cell. Physiol., in press].