Configurations of a polymeric antigen adsorbed to a B-cell membrane

Abstract

Thymus-independent antigens that can stimulate B cells in the absence of T cells are polymeric molecules with repeating arrays of antigenic determinants. Immunological studies of the activity of haptenated thymus-independent antigens have shown that small changes in hapten density can transform a polymeric antigen from non-immunogenic to immunogenic, and from immunogenic to tolerogenic. Such studies seem to indicate that the structure of the polymer, when bound to a B cell, is important in determining immunological responses. In this paper we compute the equilibrium configuration of a linear, haptenated polymer adsorbed to a cell surface, and correlate configurational features of the molecule with its immunological functioning. When a polymeric molecule is bound to a cell the whole molecule is not tied to the surface; rather there are sections which form loops extending into solution, and other sections, trains, which are bound tightly to the surface. The trains cross-link antibody receptors on the B-cell surface in a fashion which restricts their mobility in the plane of the membrane. We call this type of cross-linking restrictive. Our computation of equilibrium polymer configurations shows that there is a critical hapten density, below which the polymer does not bind to the surface. At hapten densities slightly above the critical density, the polymer binds weakly to the surface with a configuration dominated by few, rather long loops. These loops cross-link receptors, but do so without bringing the cross-linked receptors into close proximity and without substantially restricting their motion. Long loops thus cause unrestrictive cross-linking. As the hapten density increases, the average loop length decreases and the average train length increases. Thus cross-linking becomes restrictive. In this density range immune stimulation is observed. At high hapten densities long trains form, separated by few, very short loops and almost all receptors are cross-linked. Consequently cross-linking may be overly restrictive, freezing receptors into place and generating an abundance of cross-linking or other signals which induce a state of immunological tolerance.