A New Approach to the Study of Human B Lymphocyte Function Using an Indirect Plaque Assay and a Direct B Cell Activator

The understanding of the human immune system has been governed by technical developments. The description of electrophoresis and immunoelectrophoresis allowed the monoclonality and class specificity of myeloma proteins to be analyzed, and the recognition of agammaglobulinaemia. The description of myelomas aided development of the clonal selection theory and the variety of agammaglobulinaemias allowed speculation about lymphoid differentiation. In the humoral limb of the immune response the next major development was the discovery of B lymphocyte surface markers (Moller 1961, Coombs et al. 1969, Dickler & Kunkel 1972), which allowed characterization of B lymphocyte populations in ontogeny, immunodeficiency and leukemias (Cooper et al. 1973, Seligmann 1973). Surface markers in resting cells have proved to be poor indicators of B cell function since many agammaglobulinaemias bear a normal complement of resting B cells which are, however, unable to synthesize immunoglobulin. Functional analysis of B lymphocyte populations in murine systems has been greatly facilitated by the use of polyclonal B cell activators (PBA) to provide a nonspecific stimulus to maturation and immunoglobulin synthesis of large number of clones and by the use of the plaque assays as a sensitive technique for detection of antibody synthesis at the cellular level. Pokeweed mitogen (PWM) has been the most studied human B cell mitogen and its use has yielded valuable information in agammaglobulinaemia and in human B lymphocyte ontogeny. Activation has been assessed by morphological blast formation, cytoplasmic immunoglobulin synthesis or released immunoglobulin