Immunoregulation by processed immunoglobulin on B-cells.
According to Jerne's network hypothesis, the unique amino acid sequences of Ig variable regions, that is, the idiotypic determinants can function in immunoregulatory mechanisms and cellular interactions. Indeed, Id-specific T-cells (mostly CD4+) have since been described, but the nature of Id-positive Ig on B-cells involved in recruiting T-cells is unclear. Studies from our ongoing investigation presented here clearly show that Id can evoke both CD4+ and CD8+ T cells, and exist not only as the integral components of a bona fide antigen-binding receptor Ig but also as distinct molecular entities in processed forms on the cell surface of B-lymphocytes. Using a B-cell hybridoma, 2C3, that expresses anti-hapten (phthalate) antibody receptors on the cell surface, we induced both Id-specific CD4+ and CD8+ T effector cells. The CD4+ T cells were suppressive and mediated generation of Id-loss 2C3 variants, whereas CD8+ T cells were highly cytotoxic and selectively eliminated 2C3 cells both in vitro and in vivo. These effector cells could be induced by cell membrane-associated Ig but not by its soluble form, secreted by 2C3 cells. Antibodies to MHC class I but not class II molecules were inhibitory to this induction. Furthermore, brefeldin A (BFA), an inhibitor of MHC class I mediated processing, blocked induction of CTL but had no effect on the expression of membrane Ig. Moreover, chloroquine, an inhibitor of class II-mediated processing, had no effect. A few reports have recently appeared indicating that an exogenous Ig can be processed by B-cells in the context of MHC class II proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
Ghosh
S K
SK
Department of Life Sciences, Indiana State University, Terre Haute 47809.
Chakrabarti
D
D
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D006825:Hybridomas / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D012515:Mast-Cell Sarcoma / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015704:CD4 Antigens; D016827:CD8 Antigens; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region