Mapping of antibody specificities to V H gene families

V _H gene segments represent the products of the repeated duplication and subsequent diversification of a primordial V gene element. It is widely assumed that natural selection, operating via pathogens, has played the dominant role in this process. Here, we screen some 3.7 × 10⁴ C ⁺ colonies of mitogen-activated B cells for the production of antibodies specific for phosphorylcholine or hen egg lysozyme and expression of the V _H X-24, S107, Q52, or J558 gene families. These gene families were expressed at frequencies proportional to their genomic complexity among both unselected and antigen-specific C ⁺ colonies. Thus, the capacity to encode equivalent antibody-combining sites is dispersed uniformly among V _Hfamilies. This result suggests that individual V _H genes have not evolved to address specific antigens.