III . B Cell Plasma Membrane Depolarization and Hyper - Ia Antigen Expression Induced by Receptor Immunoglobul in Cross - linking Are Coupled

We have previously reported B lymphocyte plasma membrane depolarization resultant from receptor immunoglobulin cross-linking by anti-immunoglobulin (1) and specific antigen (2). These findings extend observations of Taki (3) and Kiefer et al. (4), who have reported an early decrease in the plasma membrane potential ofT and B lymphocytes in response to mitogens. The mutually exclusive induction of depolarization in T and B cells by concanavalin A (Con A) ~ and lipopolysaccharide (LPS) respectively, and the failure of LPS-unresponsive C3H/ HeJ B cells exposed to LPS (5) to undergo membrane depolarization suggests that changes in ion flux manifest by decreased membrane potential may be important in mitogenesis. In other somatic cell systems (6-9), plasma membrane depolarization has been demonstrated to be important for activation and entry into cell cycle, and has further been postulated to be an initial and critical event in these processes. Our studies (1, 2) indicate that while there is a strong correlation between depolarization and entry into cycle by B lymphocytes in response to mitogens, anti-immunoglobulin, and thymus-independent antigens (TI), plasma membrane depolarization is itself an insufficient signal to support transition from Go to G~. This conclusion is based upon results that demonstrate that while thymus-dependent (TD) antigens (2), 50 mM K ÷ (10), and phorbol diesters (11) are able to facilitate decreased plasma membrane potential, none stimulate a significant proportion of cells to undergo Go to G~ transition. In view of the distinction observed between TD and TI antigens, it is possible that membrane depolariation is a manifestation of but one of multiple signals required for B cell activation.