Activation and cell cycle control of murine B lymphocytes

The cell cycle of activated murine B lymphocytes (B cells) is controlled by the occupancy of surface membrane-bound immunoglobulin (Ig) and by two types of growth factors, called alpha and beta factors. These growth factors are produced in an endocrine fashion by the interaction of helper T lymphocytes (T cells) with antigen-presenting macrophages (A cells). Antigen is taken up, processed and presented on the surface of A cells in the context of class II major histocompatibility complex (MHC) glycoproteins. Helper T cells recognize this association of antigen and class II MHC molecules. A cells produce alpha factors and T cells produce beta factors. The molecular nature of these factors and of the corresponding receptors on B cells has yet to be elucidated, although it can be shown that the complement component C3d replaces alpha factor action. Resting, G0 phase B cells are refractory to the action of alpha and beta factors. They have to be excited, i.e. rendered susceptible to the action of these factors. This can be achieved by the interaction with helper T cells that recognize antigen, bound by surface membrane Ig, in the context of class II MHC glycoproteins on the surface of resting G0 B cells. Excitation can also occur in a polyclonal fashion by cross-linking of surface Ig with immobilized, Ig-specific antibodies, or by the interaction with polyclonal activators of B cells, such as lipopolysaccharides. Entry into the cell cycle is asynchronous. Activated, cycling B cells can be synchronized by size separation, using velocity sedimentation. Synchronized B cells will retain their synchrony for several divisions, when they are stimulated by immobilized Ig-specific antibodies, alpha and beta factors. They divide every 20 h at 37 degrees C. Omission of either of the three stimuli arrests B cells, though at different points in the cell cycle. Three restriction points are found: the first occurs immediately after mitosis and is controlled by the binding of immobilized Ig-specific antibodies to surface membrane-bound Ig.(ABSTRACT TRUNCATED AT 250 WORDS)