Hapten-specific hemolytic plaque assays usually fail to detect most of the diversity in the anti-hapten response.

Immunization of rabbits or mice with a single, chemically defined hapten elicits populations of plaque-forming cells (PFC) detectable not only on sheep erythrocytes (SRBC) bearing the immunizing hapten, but also on SRBC bearing structural analogues of the immunizing hapten. Most of these analogue-reactive PFC preferentially lyse analogue-conjugated SRBC and cannot be detected on erythrocytes bearing the immunizing hapten. Thus, they represent heretofore largely unstudied components of the secretory B-cell response to haptenic immunization, and they have been termed alloreactive PFC. Such alloreactive PFC are detectable using either classical small haptens or tripeptide-enlarged counterparts of these classical haptens. They are present in large numbers both in direct and in indirect PFC assays, and they are elicited in response to both thymic-dependent and thymic-independent antigens. Relatively few alloreactive PFC can be attributed to cells producing hapten-carrier or "bridge area"-specific antibodies. Since the antibodies released by alloreactive PFC can also be detected by passive hemagglutination, their presence does not appear attributable to vagaries of complement activation. Numerous coexisting alloreactive PFC populations are detectable after haptenic immunization. In early direct PFC responses it is not nucommon for a single alloreactive PFC population to outnumber the population of PFC detectable on SRBC bearing the actual immunizing hapten. These alloreactive PFC may be the source of at least some of the new "nonspecific" Ig which is formed at the time of immunization but about which little is known for lack of available techniques. Some possible implications of these findings on the specificity of B precursor cell activation are discussed.