Hypothesis for band 3 protein dynamics and NAb binding to HS RBCs with band 3 and spectrin/ankyrin deficiency.

Band 3 proteins exist in RBC membranes as preformed dimers and tetramers, of which the latter interact with ankyrin (for simplicity, only dimers are shown). These normally existing oligomers do not significantly bind anti–band 3 NAbs, presumably because the location of antigenic sites prevents their bivalent binding.49Lateral mobility and water loss result in the enhanced formation of band 3 clusters and favor bivalent binding of anti–band 3 NAbs. (A) Band 3–deficient RBCs. The excess of skeletal anchorage points compared to the reduced number of band 3 molecules in this deficiency prevents band 3 clusters from dissociation and release. This results in an increased number of IgG-opsonized band 3 clusters compared with healthy cells of the same age. (B) Spectrin/ankyrin-deficient RBCs. These membranes contain an excess of band 3 compared with skeletal anchorage points. Because band 3 clusters are primarily formed in areas detached from the skeleton, they will preferentially bud off as skeleton-free vesicles. This deprives the remaining spherocytes of bound opsonins and thereby may prolong their survival.