Figure 3.

Light chain rearrangements provide multiple pathways to the production of self-tolerant B cells. Alternative pathways are a consequence of rearrangements of the light chain loci that result in non-productive or auto-reactive BCR. Beginning with rearrangements of the κ locus on the first selected chromosome, a succession of light chains can be paired with an existing heavy chain that is already expressed on the surface of the pre-B cell. Each resulting BCR is assessed for affinity to self-antigen. Cells expressing autoreactive antibodies can be rescued via further rounds of receptor editing. If repeated rounds of rearrangements of a locus fail to generate a functional, self-tolerant antibody, and the possibilities of rearrangement are exhausted, the process may continue on other chromosomes. Rounds of κ rearrangement may be prematurely curtailed by the action of the kappa deleting element. B cells unable to generate self-tolerant antibodies despite multiple rounds of receptor editing will ultimately be deleted or rendered anergic. In contrast, B cells that generate successful light chain rearrangements that result in self-tolerant antibodies will go on to develop further into immature B cells.