In mammalian antibodies, two heavy chains link together to form a Y-shaped complex, with each arm of the Y linked to a light chain. In mice and humans, lone heavy chains are usually prevented from being secreted by a chaperone that associates with the heavy chain's constant region—the same region that links to the light chain. But the new report shows that an unusual set of fully functional heavy chain–only antibodies do get secreted.
The anomalous antibodies escaped to the cell surface because they lacked the chaperone-binding region. The secretion of these antibodies was discovered in mutant mice that lack light chain genes, but the authors also found that smaller amounts were produced in the spleen of normal mice, probably as a result of gene deletion errors during B cell development. The odd antibodies appeared to bind antigen normally and display the normal range of heavy chain diversity.
The discovery has precedence—camels and their relatives produce heavy chain–only antibodies in abundance. Light chain–deficient mice might allow the ready production of heavy chain–only monoclonal antibodies, whose smaller size lets them recognize antigen structures that elude standard antibodies. Humans might also make these antibodies in small amounts, but their relevance in vivo remains a mystery.