short time a plausible model was developed for the molecular basis of immunological specificity, and for mediation of biological function through the Fc domain. Crystallization of an IgG molecule soon followed ) confirming the inferences based on sequencing, and providing an understanding of immunological specificity at the highest level of resolution. The biological significance of these developments was encapsulated in the theory of clonal selection which holds that a B cell has on its surface immunoglobulin receptors whose antigen-binding site is identical to that of antibodies that are secreted by the cell when it encounters an antigen, and more specifically a particular B cell clone secretes antibodies with identical sequences. The final piece of the story, the Fluid mosaic model of the plasma membrane provided all the ingredients for a new model for the initiation of signal transduction; viz, receptor dimerization. The first hints of this were obtained by Becker et al who demonstrated that the extent to which human basophils—for which bivalent Immunoglobulin E (IgE) functions as a surface receptor – degranulate, depends on the concentration of anti IgE antibodies to which they are exposed, and results in a redistribution of surface molecules, which is absent when monovalent ligand is used. The latter observation was consistent with earlier findings by Fanger et al. These observations tied a biological response to events and structural details of molecules on the cell surface. A preponderance of evidence soon developed that receptor dimerization initiates responses (reviewed in ) in a variety of cell types, including B cells. Such observations led to a number of theoretical (mathematical) developments. The first of these was a simple model proposed by Bell which resolved an apparent paradox: clustering forms stable networks; i.e. binding is essentially irreversible, whereas the affinities of antibodies secreted by B cells increase as the immune response progresses. A theory of the dynamics of cell surface clustering on lymphocyte membranes was developed by DeLisi and Perelson who found the size distribution of clusters as a function of time, and its dependence on the affinity and valence of the ligand. Subsequent theories for basophils and mast cells were developed by Goldstein and Sobotka and their collaborators, all aimed at the analysis of dose-response patterns of immune cells and their biological correlates. For a recent review of clustering in immunological systems see. Ligand binding to cell surface receptors is also critical to motility, a phenomenon that