Anti- Idiotype Sera Raised

Present concepts of the maturation of a B-lymphocytic clone involve progressive changes in cellular morphology and mode of immunoglobulin (Ig) production. The ancestral small lymphocyte synthesizes Ig for insertion into its plasma membrane, while those of its descendants destined to produce humoral antibody show first a superimposed synthesis of Ig for export and finally a heavy export with little or no surface Ig apparent (1-4). In line with this apparent dichotom) of the surface and export pathways, turnover data make it unlikely that the material for export ever has a surface phase (3, 4). It is a central contention of the clonal selection theory that throughout this maturational process the variable (V) 1 regions of the Ig heavy and light chains, responsible for antibody activity and idiotypic antigenic specificity (5), remain unchanged. Experimental evidence supports this concept (6-8). Neoplasms appear to arise at various stages of B-cell maturation, developing with a restricted range of morphologies and exhibiting modes of Ig synthesis broadly in line with their normal analogues (Fig. 1). The Ig products of a single tumor might be expected to bear a uniform set of idiotypic determinants as a monoclonal hallmark. This is well established for exported Ig, in fact such products, appearing as serum monoclonal proteins, led to the first description of idiotypic specificity (9). Idiotypes on surface Ig have recently been demonstrated for those neoplasms exhibiting both surface and exported Ig. Here anti-idiotype sera raised against the exported Ig have reacted specifically with the homologous tumor cell surfaces (10-15). In one such case mice immunized against idiotypic determinants on the exported Ig of a syngeneic myeloma were thereby afforded a measure of specific protection against tumor challenge (10), presumably due to cytotoxic reactions mediated via the surface idiotypic determinants. The nonexperting neoplasms to the left of Fig. 1 provide a situation where the tumor Ig appears in extracellular fluid in only minute quantities arising from turnover on the membrane. There is thus a problem in harvesting the Ig and obtaining antisera to its presumed idiotypic determinants. However, the thera-