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

Abstract

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^1–3, V, D and J for the heavy (H) chains⁴; (2) somatic events, including mutations and gene conversion^5–8; and (3) combinatorial association of heavy and light chains^9–13, leading to the proposal that random pairing of p × H and q × L chains might generate p × q antibody molecules expressing discrete specificities. As heavy and light chains derived from the same immunoglobulin molecule would frequently reassociate preferentially^14–17, 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 V_H region, associated with distinct light chains (or vice versa) should be encountered. We report here that two heavy chains, derived from the same V_H germ-line gene, may be present in anti-NP or anti–GAT antibodies, depending on their association with a specific λ or κ light chain, respectively.