Aggregates, Crystals, Gels, and Amyloids: Intracellular and Extracellular Phenotypes at the Crossroads of Immunoglobulin Physicochemical Property and Cell Physiology
Schematic representation of the relationship between individual IgG clones’ biosynthetic requirements and intrinsic cellular capacity. (a) In this hypothetical setting, two IgG clones 1 and 2 have different levels of resource requirements during biosynthesis (shown in the vertical axis). The cells have sufficient capacity to support clone 1’s biosynthesis, but do not have the capacity to meet the requirement of clone 2. Clone 2 ends up aggregating into Russell body (RB). (b) The same pair of clones were expressed in the same cell background. In this hypothetical setting, however, the cells have lost a part of their capacity due to stress, senescence, pathological changes, and so forth. As a result, both IgG clones come to develop RB phenotypes. (c) An example of successful protein engineering that reduced the biosynthetic requirements of IgG clone 2. Engineered clone no longer induces RB in the same cell host. (d) In this setting, cell phenotype engineering strategies increased the overall capacity of the cell host. The clone 2 no longer forms RB in the engineered cell host.