Doubling Up Antibody Specificity

Science  14 Sep 2007:
Vol. 317, Issue 5844, pp. 1465j
DOI: 10.1126/science.317.5844.1465j

The light and heavy chains that make up antibodies both carry variable regions at their ends that combine to form the highly diverse antigen-binding sites of the antibody molecule. Immunological dogma states that a single B cell generates antibodies of one defined specificity (each molecule carries identical, symmetric heavy-light chain combinations), but one particular class of antibody known as immunoglobulin G4 (IgG4) has been suspected of breaking this rule. Van der Neut Kolfschoten et al. (p. 1554; see the Perspective by Burton and Wilson) now provide direct evidence that IgG4 can swap a heavy-light combination on one fragment antigen-binding arm for another, which creates antibodies with dual specificity. Furthermore, in a model of disease that relies on cross-linking by antibodies, the loss of single specificity (and the loss of the ability to cross-link) was effective at reducing disease.

Navigate This Article