The majority of B lymphocytes in the immune system are resting cells. When antigen enters the system it stimulates to replication and maturation to antibody (immunoglobulin, Is) secretion those B cells that possess antigen-specific Ig molecules on their surface membrane. One B cell produces only one type of Ig molecule in many copies. The wide variety of different Ig molecules with different antigen recognition capacities is therefore a consequence of a wide variety of different B cells producing them [ 1, 21.
Although the selection of B cells is initiated by the binding of antigen to surfacebound Ig molecules, this binding appears insufficient for stimulation to replication and maturation-ie, to an immune response of B cells [3, 41. B cells must cooperate with other cells, such as T cells and macrophages [5-71 or with mitogens often produced by bacteria [&lo] to be stimulated. Functionally synonymous with the term "macrophage" the following terms are often used and will be used in this paper: accessory cell, antigen-presenting cell (APC), adherent cell, irradiated spleen cell, and peritoneal exudate cell. Depending on whether T cells are needed for stimulation or not, B cell stimulation is called T cell-dependent or T cell-independent. T celldependent B cell stimulation was found to be restricted in its functioning by products of genes encoded in the I region of the H-2 complex [ 111. It is now clear that such H-2 restriction operates at two levels of cellular cooperation. At the first level T cells (called 'helpers') recognize antigen in the context of Ia determinants on macrophages [ 121. B cells and B-lymphomas expressing Ia-determinants have also recently been found to be functioning at this level of cooperation [ 131. The cooperation leads to