Antigen presentation by hapten-specific B lymphocytes. I. Role of surface immunoglobulin receptors.

The present study examines the ability of hapten-specific murine splenic B lymphocytes to present hapten-proteins to carrier-specific T cell hybridomas. BALB/cB cells specific for 2,4,6-trinitrophenyl (TNP) were isolated from spleens of immune mice by elution from TNP-gelatin-coated dishes. Such cells presented the TNP-modified terpolymer, GL phi, at concentrations as low as 0.1 microgram/ml, to a GL phi-specific, I-Ed-restricted, interleukin 2-producing T cell hybridoma. In contrast, the same B lymphocytes required 1,000-fold higher concentrations of unmodified GL phi to stimulate the same T cell hybridoma. The presentation of low concentrations of TNP-GL phi by TNP-specific B lymphocytes was significantly or completely blocked by anti-Ig antibody or TNP-proteins, indicating that surface Ig receptors were critically involved in this phenomenon. Finally, binding of TNP-proteins did not alter the ability of the B cells to present unrelated, unhaptenated proteins or to stimulate alloreactive T cells. These results suggest that surface Ig receptors serve to focus antigens onto specific B lymphocytes and that such cells are highly efficient at presenting linked antigenic determinants to T cells. The implications of these findings for the mechanisms of physiologic, histocompatibility-restricted T-B collaboration are discussed

Inhibition of T-lymphocyte-mediated tumor-specific lysis by alloantisera directed against the H-2 serological specificities of the tumor

After appropriate in vivo or in vitro immunization, cytotoxic T lymphocytes (CTL) are generated which efficiently kill cells bearing particular membrane antigens in common with the immunizing cell (reviewed in reference 1). Such CTL have been most thoroughly studied in mice, employing alloimmunization with cells differing at the major histocompatibility locus, H-2. in such cases, the predominant cell surface antigens recognized by the CTL appear to be the molecules carrying the serologically defined H-2 specificities, coded for by the K and D regions of the H-2 complex (2). In other syngeneic models of cell-mediated specific cytolysis, involving lymphocyte chariomeningitis (LCM) virus- or ectromelia virus-infected cells or TNP-modified lymphoid cells, thymus-derived cells also constitute the main effector cell type. The CTL generated in these latter systems function most efficiently when virus-infected or TNP-modified target cells share identitites at the H-2K or H-2D loci with the effector CTL and stimulator cells (3-5). Another set of experimental systems in which CTL are generated and play a significant biological role is that of immunity to tumor-associated antigens (TAA) (6). The nature of the TAA which the CTL recognize is only beginning to be understood. Several recent reports indicated the existence of physiochemical and/or antigenic relationships between TAA and H-2 antigens (7,8). These relationships, together with the genetic restrictions cited above in the generation of CTL involving products of the H-2K or H-2D loci suggested the possibility that in certain tumor systems, the TAA which are able to most effectively stimulate CTL responses might be structurally similar to, or linked with, the H-2K or H- 2D molecules on the tumor surface. It has been previously demonstrated in allogenic models that antisera specific for the appropriate H-2K or H-2D products present on a target cell could specifically block CTL-mediated lysis (1,9). This report demonstrates that certain anti-H-2 alloantisera specific for the target tumor cells can block lysis of those target cells mediated by syngeneic tumor-specific CTL effector cells