Editing the immune system

B lymphocytes that produce antibodies recognizing self antigens are tolerized by a process of clonal selection, which involves clonal deletion, anergy and a gene-recombination event called receptor editing. In the February 23 Science, Casellas et al. describe a model mouse system for investigating the importance of receptor editing (Science 2001, 291:1541-1544). They generated a polymorphic immunoglobulin kappa allele by replacing the mouse kappa constant (mCkappa) region with the human sequence (hCkappa). Flow cytometry and mRNA analysis allowed them to monitor receptor editing in various genetic crosses. Casellas et al. provide evidence for extensive editing (about 25% of immunoglobulin light chains on the surface of B cells). Furthermore, they demonstrate that B cells which are undergoing editing are specifically delayed (for at least two hours) in the small pre-BII-cell stage during development.