Models for the dynamics and order of immunoglobulin isotype switching

Experiments show that class switch recombination (CSR) depends on the number of divisions that the cell has performed rather than on the time since stimulation. Using computer simulations of CSR dynamics in B cell populations, we addressed the following questions. How does the probability of CSR depend on the number of divisions that a cell has performed? How does the cell decide which isotype to switch to? Does this decision depend on the distance between the genes of the pre-switch and the post-switch isotype? Our results indicate that post-switch isotype choice may be determined indirectly by the probabilities of division (which is fixed) and of switching per division (which increases as a function of the number of divisions that a cell performs), and more directly by a bias in the choice of the post-switch C gene segment towards those proximal to the pre-switch C gene.