A primary humoral immune response to most antigens results in the development of a long-lasting state of immunity. In addition to influencing the outcome of a secondary immune response to the priming antigen, this state of immunity may also alter subsequent immune responses to antigens that are structurally related to this priming antigen, a phenomenon that has been termed "original antigenic sin" (1-3). This crossreactive property of immunity results in the "immune history" of an animal having a direct bearing on its "immune status" to antigens that may be encountered in the future.Molecular analyses of hybridomas isolated at various stages of humoral immune responses indicate that both the clonal composition of the responding B cell population and the structure and function of the antibodies expressed by this population vary with time (4). Isotype switch recombination results in changes in antibody constant (C) region structure and somatic hypermutation results in alteration of variable (V) region structure. A progressively stringent process of antigen selection also acts on the responding B cell population, resulting in the affinity maturation of expressed antibodies (5). It has been proposed that such "somatic evolution" of antibody structure is requisite for the formation of the memory B cell population (6). Moreover, it has been suggested that the longevity of humoral memory may result from the structural constancy ofthe antibodies expressed by memory B cells, as well as the clonal stability of this population of cells (7,8). If this is true, then the "immune status" of an animal to a given antigen may be strongly influenced by the antibody structures that have been generated during previous immune responses to other antigens .To directly examine how the memory B cell population elicited to one epitope might be used during subsequent immune responses to other, structurally related epitopes, we have explored the phenomenon oforiginal antigenic sin at a molecular level. During the immune response of A/J mice to p-azophenylarsonate (Ars)I a family of antibodies encoded by a single VH gene segment (VHId°R) is reproducibly

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