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.
Louzoun
Yoram
Y
402 Schultz Laboratory, Department of Molecular Biology, Princeton University, Washington Road, Princeton, NJ 08544, USA. ylouzoun@princeton.edu
Friedman
Tzivia
T
Luning Prak
Eline
E
Litwin
Sam
S
Weigert
Martin
M
D000465:Algorithms; D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D007132:Immunoglobulin Isotypes / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D018448:Models, Immunological; D015233:Models, Statistical
D007132:Immunoglobulin Isotypes