Idiotypic IGM on a B-Cell Surface Requires Processing for Recognition by Anti-idiotypic T Cells

Abstract

Immunization with purified idiotypic IgM derived from the BCL, lymphoma generates CD4-positive T cells which proliferate specifically in response to idiotypic antigen expressed at the surface of the BCL 1 tumor cells. These T cells have been hybridized and two cloned hybridomas have been used to study the molecular nature of the idiotypic antigen recognized. Endogenous presentation of idiotype by the B cells generated IL-2 from the T-cell hybridomas, as measured by a CTLL response. Presentation was inhibited in a dose-dependent manner by chloroquine or ammonium chloride, both of which affect proteolytic degradation of antigen in the endosomes. Similar results were obtained with inhibitors of metabolism or protein synthesis. However, none of these reagents affected expression of idiotypic IgM at the cell surface under the conditions used, indicating that whole IgM is not interacting directly with the T-cell receptor. Interaction between the presenting B cells and T-cell hybridomas was inhibited by anti-CD4 and, in one case, by a monoclonal antibody directed against a determinant in the I-E d region of the MHC Class II. Inhibition also occurred with antibodies against IgM, either anti-constant region or anti-idiotype, and the univalent Fab'γ fragment was an effective inhibitor. These data indicate that the B cell constitutively presents its endogenous idiotypic immunoglobulin to CD4-positive T cells following endocytosis from the surface, proteolytic degradation, and interaction with MHC Class II molecules. This endogenous pathway is perturbed by binding of exogenous anti-immunoglobulin antibody, perhaps mimicking what might occur when surface immunoglobulin encounters antigen.