Two monoclonal antibodies against different antigens using the same VH germ-line gene

Immunoglobulin diversity seems to arise largely by three mechanisms: (1) the existence of several germ-line genes, which must be rearranged before expression--that is, V and J for the light (L) chains, V, D and J for the heavy (H) chains; (2) somatic events, including mutations and gene conversion; and (3) combinatorial association of heavy and light chains, leading to the proposal that random pairing of p X H and q X L chains might generate p X q antibody molecules expressing discrete specificities. As heavy and light chains derived from the same immunoglobulin molecule would frequently reassociate preferentially, it is likely that only a fraction of potential heavy--light pairs actually provides "valid' antibodies. As a consequence of combinatorial heavy--light chain pairing, antibodies of discrete specificities sharing the same VH region, associated with distinct light chains (or vice versa) should be encountered. We report here that two heavy chains, derived from the same VH germ-line gene, may be present in anti-NP or anti--GAT antibodies, depending on their association with a specific lambda or kappa light chain, respectively.