Analysis of B cell receptor production and rearrangement. Part I. Light chain rearrangement.

A probabilistic model of allelic exclusion fails to explain the status of receptor genes and the receptor phenotype of most B cells. A large proportion of B cells have incompletely rearranged H and/or L chain genes (e.g. kappa0/kappa+) and most B cells express only one receptor. These properties seem to require deterministic features of B cell development such as special mechanisms that stop rearrangement. However, receptor editing has revealed that rearrangement-stop is not stable and that multi-receptor lymphocytes make up a significant fraction of certain B and T cell populations. Consequently we have revived the purely probabilistic approach in a model that now includes receptor editing and allows for some multi-receptor B cells. We find that this model can explain the observed properties of B cells when the frequency of self-reactive B cells is high. Indeed, as we illustrate for anti-DNA, this is the case. Hence the probabilistic model has life and assiduous use of the model suggests unexpected but not unrealistic features of lymphocyte development.