Poor repertoire selection in symmetric idiotypic network models.
The selection of B and T cell repertoires is known to be influence by idiotypic interactions during early ontogeny. Early B cell clones are multi-specific, have numerous idiotypic interactions, produce IgM antibodies, and may constitute a separate cell lineage (characterised by the Ly1 or CD5 marker). Furthermore, because early B cells are self-reactive, self antigens should play a crucial role in the repertoire selection. Previously we developed a theoretical model of idiotypic B cell interactions. The model is based on a (symmetric) bell-shaped interaction function. The symmetry and the shape are a consequence of the process of receptor crosslinking. Assuming that early (i.e. IgM) B cell interactions are independent of helper T cell activation, we now apply this model to the problem of idiotypic repertoire selection. In the model the molecular structures of B cell receptors (i.e. of the idiotypes) and of self antigens are represented by random (bit)patterns. Interactions are based on complementary matches between these patterns. Therefore, the repertoire selection is brought about by stimulatory networks based upon complementary matches. These results show that the presence of a self antigen specifically shapes the B cell repertoire. The selection depends on the nature of the antigenic signal; we incorporate either stimulatory or inhibitory (i.e. tolerizing) self antigens. Clones stimulated by the self antigen tend to become aggressive in the network; tolerized self-reactive clones tend to become suppressed. Thus, idiotypic interactions play a facilitating role in self/non-self discrimination. However, since the idiotypic selection is only a tendency, the immune system should not rely on it. We next incorporate two classes of B cells. We call them the early, or "IgM", and the late, or "IgG", B cells (IgG B cells appear after the development of the IgM repertoire). IgG B cells may have only a few idiotypic interactions. We investigate whether the early IgM repertoire, which is (partly) selected by self antigen, influences the selection of the late IgG repertoire. It turns out that this influence can only be non-specific. Either we find a similar tendency in the IgG repertoire, or we find that the IgG repertoire influences the IgM repertoire non-specifically. Thus, despite the fact that this theoretical work readily confirms empirical results showing that the manipulation of early idiotypic interactions can have specific and long-lasting effects, the presupposed physiological role of these interactions, in terms of self-reactivity or repertoire selection, fails to develop in our models.
De Boer
R J
RJ
Bioinformatics Group, University of Utrecht, The Netherlands.
D000818:Animals; D000916:Antibody Diversity; D000918:Antibody Specificity; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D015322:Gene Rearrangement, B-Lymphocyte; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D008954:Models, Biological; D008968:Molecular Conformation; D011947:Receptors, Antigen, B-Cell / Q000276:immunology
D001324:Autoantigens; D000939:Epitopes; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell