Editing disease-associated autoantibodies - PubMed (original) (raw)
Editing disease-associated autoantibodies
C Chen et al. Immunity. 1997 Jan.
Free article
Abstract
We have generated site-directed transgenic mice whose transgenes code for anti-DNA antibodies. These antibodies are representative of the lupus-associated anti-DNAs seen in mouse models of autoimmunity and human SLE, and have the usual characteristics of pathogenic autoantibodies. As conventional transgenics in nonautoimmune mice, anti-DNA B cells have been shown to be deleted or inactivated. Autoreactive B cells can also escape negative regulation by a process called receptor editing. Here we describe two combined immunoglobulin H and L chain site-directed transgenic mouse models and characterize their editing phenotypes. One model, 3H9R/Vkappa4R, has a deletion-prone phenotype and undergoes editing, primarily by inactivation of the light chain by leap-frogging events. In the other model, 3H9R/Vkappa8R, B cells are susceptible to anergy and maintain most of their HR and LR chains. These studies clarify the relationship between editing and other mechanisms of tolerance.
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