CROSS-LINKING RECONSIDERED - BINDING AND CROSS-LINKING FIELDS AND THECELLULAR-RESPONSE

We analyze a model for the reversible cross-linking of cell surface re ceptors by a collection of bivalent ligands with different affinities for the receptor as would be found in a polyclonal anti-receptor serum . We assume that the amount of cross-linking determines, via a monoton ic function, the rate at which cells become activated and divide. In a ddition to the density of receptors on the cell surface, two quantitie s, the binding field and the cross-linking field, are needed to charac terize the cross-linking curve, i.e., the equilibrium concentration of cross-linked receptors plotted as a function of the total ligand site concentration. The binding field is the sum of all ligand site concen trations weighted by their respective binding affinities, and the cros s-linking field is the sum of all ligand site concentrations weighted by the product of their respective binding and cross-linking affinity and the total receptor density. Assuming that the cross-linking affini ty decreases if the binding affinity decreases, we find that the heigh t of the cross-linking curve decreases, its width narrows, and its cen ter shifts to higher ligand site concentrations as the affinities decr ease. Moreover, when we consider cross-linking-induced proliferation, we find that there is a minimum cross-linking affinity that must be su rpassed before a clone can expand. We also show that under many circum stances a polyclonal antiserum would be more likely than a monoclonal antibody to lead to cross-linking-induced proliferation.