Influence of the Macromolecular Form of a B Cell Epitope on the Expression of Antibody Variable and Constant Region Structure by Suzanne Fish and Tim Manser

Molecular analyses of murine humoral immune responses have been largely limited to responses induced by soluble proteins, polysaccharides, and hapten conjugates thereof (1-15) . However, in nature the mouse rarely encounters an antigenic structure in association with such chemically simple forms, but rather in association with a viral particle, bacterium, or parasite . How such differences in the macromolecular form of an epitope affect the structural outcome of the humoral immune response to that epitope is not well understood . Antigens may differ in their humoral immunogenic properties due to differences in epitope valence, solubility, mitogenic qualities, stability, degree of T cell independence, adjuvant properties, and ability to be phagocytized by macrophages . Any one of these factors could influence the structure of antibodies elicited to an epitope on the antigen due to resulting differences in the degree of participation in the immune response of T cells, accessory cells, or B cells that are members of functionally distinct subsets or reside in particular lymphoid microenvironments . Indeed, a number ofinvestigations (2, 16-21) have revealed that the isotypic profile of serum antibodies elicited to haptens can vary dramatically depending on the molecular form of the haptenic determinant . Haptens conjugated to soluble proteins often elicit antibodies mainly of the IgG1 class, while the same haptens conjugated to polysaccharide often elicit IgM and IgG3 (2, 16, 17, 19). The immune response to viruses is nearly exclusively composed of IgG2a (22), and the immune response to many parasites is composed predominantly of IgE (23, 24). These data demonstrate that the various isotypic forms of Ig are not selected at random for expression but that the immune system is capable of distinguishing amonga variety of macromolecular forms ofan epitope and regulating expression of the antibody isotypes elicited to that epitope in response to such differences . In contrast to the information available on the effects of antigenic form on the expression of Ig isotypes, little is known (2, 25, 26) about how this influences expression of particular antibody variable region structures . While the antigenic specificity of a V region clearly plays a role in the clonal selection process, it is not understood whether the V region structural outcome of an antigen-driven