Evidence for two distinct activation states available to B lymphocytes

The sites and modes of action of several B cell mitogens and interleukins were examined. Cell cycle analyses of B cell responses to several polyclonal activators including LPS, DXS, LPS plus DXS, and anti-immunoglobulin were performed. Two different states of B cell activation distinguished by RNA content, DNA content, and cell size were observed. LPS promoted transitions throughout the cell cycle, whereas DXS primarily caused exit from G0. Synergy between LPS and DXS was observed in elicitation of exit from G0. Activation by anti-immunoglobulin was found to be influenced by the antibody dose and the cell density of culture. Interleukins could influence anti-IgM-induced responses by increasing G0 exit, and by increasing commitment to DNA synthesis. A model of B cell activation in which cells are stimulated to a stage with intermediate RNA levels (G1A) by polyclonal activators is suggested. Some interleukins appear to be involved in this process. At G1A, cells are receptive to signals delivered by interleukins or some polyclonal activators that drive them to late G1 and DNA synthesis. After cell division, cells re-enter G1A in which interleukins or mitogens are necessary for a continued response.