Abstract
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. κ 0/κ+) 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.
Original language | English |
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Pages (from-to) | 169-190 |
Number of pages | 22 |
Journal | Seminars in Immunology |
Volume | 14 |
Issue number | 3 |
DOIs | |
State | Published - Jun 2002 |
Externally published | Yes |
Keywords
- Allelic exclusion
- Antibody
- B cell receptor
- Clonal selection hypothesis
- Gene rearrangement
- H/L STOP
- Immunoglobulin
- Isotypic exclusion
- Light chain
- Probabilistic model