It is now well known that B cells characteristically express immunoglobulin receptors on their surface. On average, each B lymphocyte bears approximately 10^ immunoglobulin molecules on its outer cell membrane. A relatively small portion of the carboxy terminal end of the immunoglobulin molecule is embedded in the fluid membrane, and the rest of the surface antibody receptor is exposed. Since these receptors for antigen are intimately involved both in antigen triggering of the immune response and in the induction of specific immune tolerance, it is perhaps not surprising that cross-linkage of surface immunoglobulins with divalent; mti-Ig antibodies may have either positive or negative effects.

Our studies of the effects of anti-Ig antibodies have been concerned chiefly with their inhibitory effects on B cells. We have used antibodies specific for immunoglobulin isotype and allotypic determinants to examine different stages in the life history of B cells. These studies, conducted in chickens, mice, rabbits and humans, led directly to demonstration of the existence of an immature IgM* B lymphocyte whose development is easily blocked by cross-linkage of surface IgM molecules and which has the capacity to give rise to B cells which produce other immunoglobulin isotypes. Indirectly these studies led to the identification of a very immature cell type of B lineage in mammals, the so-called pre-B cell, which has the unusual feature of expressing;/chains only in the cytoplasm, ie, surface immunogiobulin receptors are lacking. It is during this stage in differentiation that allelic exclusion is expressed and the process of clonal diversity is initiated.