A theory of allelic and isotypic exclusion for immunoglobulin genes

Heavy (H) chain binding protein (BiP), which binds to free immunoglobulin H chain of the mu and gamma classes, can be demonstrated in pre-B-cells. It is proposed that the displacement of BiP from H chain by light (L) chain terminates the activity of the enzyme system, L-generase, which catalyzes DNA rearrangement at the L chain loci, generating the complete gene which may or may not be functional. This ensures allelic and isotypic exclusion for the L chain loci. It is further proposed that those cells that productively rearrange both alleles at the H chain locus are eliminated by the "H chain toxicity" effect.