•Allelic
exclusion: expression of only one allele in a diploid cellè one lymphocyte expresses one
antigen receptor (ie, productive rearrangement of both heavy and light chains).
•
•To prevent two alleles of each immunoglobulin from making a productive joint,
once an allele has a productive joint, the cell ceases current stage of
rearrangement and goes to the next stage.
•
Probability of generating a pre-B cell:
theoretical: 1/3+(2/3x1/3)=55%
Actual frequency is lower: V genes
contains pseudogenes
• Halting further rearrangement.
Two mechanisms:
•
(1).Inactivation
of RAGs
- Phosphorylation of RAG-2è via the pre-B receptor è degradation
- mRNA synthesis of RAG-1 and RAG-2 is
repressed
(2).Inaccessibility
of recombinase to heavy chain gene segments (later)