INTERACTION OF B-CELL RECEPTORS AND ANTIGENS WITH DIFFERENT SPATIAL ARRANGEMENT

Abstract

Abstract. B-cell receptors can interact with antigen epitopes on various objects: macromolecules, microorganisms or on the surface of other cells, for example follicular dendritic cells. Accordingly, B cells, on the one hand, have the ability to evaluate the location of epitopes on the surface of a pathogen, and, on the other hand, they must adapt their receptor apparatus to different epitope locations and antigen-bearing surface properties. Indeed, B-cell receptors, antibodies and other multimeric molecules of the immune system better bind objects to the regular and dense arrangement of epitopes characteristic of many pathogens. As a result, this arrangement of epitopes can be recognized by the immune system as a pathogen-associated geometric pattern, but the conditions for its recognition by B cells change depending on the isotype of the immunoglobulin in the receptor and the degree of maturity of the B lymphocyte. Young B cells express membrane IgM, which is involved in the development of B cells and the selection of their repertoire. Receptors with IgM do not impose strict requirements on the location of epitopes and can activate the B cell even when binding a monovalent antigen. Receptors with membrane IgD are expressed later and predominate on naive B cells before entering the immune response. These receptors are optimized for point-to-point antigen binding and severely require this type of interaction to induce an activation signal. Before contact with antigen, B-cell receptors are grouped in discrete zones of the membrane - nanoclusters, due to close interactions with the actin cytoskeleton. Receptors with membrane IgM and IgD form separate nanoclusters, with IgD located on lipid rafts together with co-receptors and signaling molecules, while IgM are located at normal membrane sites. Contact with the antigen leads to the disconnection of receptors from the cytoskeleton, the growth of their mobility and the unification of nanoclusters into microclusters - large clusters enriched with signal molecules. The most dynamic changes are observed by contact with an antigen fixed on the membrane of another cell. In this case, free actin moves to the periphery of the intercellular contact zone, where it forms the cytoskeleton of the processes carrying the clusters of receptors. The processes spread across the surface of the partner cell and then contract, moving the antigen-binding microclusters to the center of the contact zone. Finally, the microclusters combine into a central cluster of the immune synapse, the intensity of the activation signal drops, and the cell prepares for endocytosis of antigens grouped at the local site. Thus, the structure of B-cell receptors can contribute to the response of the B-lymphocyte to antigens with a characteristic spatial location, while the dynamic interaction of the B-cell receptor apparatus with the cytoskeleton allows optimizing the binding of antigens presented on various carriers. Knowledge of the spatial aspects of antigen recognition may be useful for the construction of vaccines based on virus-like particles or antigens on other artificial carriers.