The discovery of immunoglobulin heavy chain binding protein (BiP) in antibody-producing cells (Morrison and Scharff, 1975; Haas and Wabl, 1984) had researchers trying to assign an immune function to it. In one theory, BiP was thought to regulate allelic exclusion of heavy and light chain genes (Wabl and Steinberg, 1982). Part of the theory assumed that BiP neutralized a proposed heavy chain toxicity. If a cell was making heavy chains improperly from both alleles, then there would not be enough BiP to go around and the cells would die and be eliminated from the B lymphocyte pool.
But John Kearney (University of Alabama, Birmingham, AL) had been working with pre–B cell hybridomas that only produced heavy chains yet suffered no toxic effect, so he questioned the toxicity idea. He started by making a BiP antibody. The unexpected endpoint would be the competitive area of chaperone...
