Systems and methods are disclosed herein that enable computer-implemented modeling of lymphocyte differentiation and developmental processes. Cell-based models and methods for simulating natural and transgenic lymphocyte differentiation are also disclosed. In some embodiments, systems and methods are provided for cell-centric simulation of lymphocyte differentiation with accommodating virtual thymic and/or bone marrow environment feedback. In one embodiment, a computer-implemented method of modeling lymphocyte differentiation can include receiving configurable simulation information and initializing an ontogeny engine to an initial step boundary in accordance with the configurable simulation information. The method can also include advancing the ontogeny engine, until a halting condition is encountered, from a current step boundary to a next step boundary in accordance with the configurable simulation information and the current step boundary. The initial step boundary can define at least one virtual early lymphoid progenitor cell. The advancing can include performing a stepCells function.