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Antibodies that bind complex glycosaminoglycans accumulate in the Golgi.

ABSTRACT: Light (L) chains that edit anti-DNA heavy (H) chains rescue B-cell development by suppressing DNA binding. However, exceptional editor L chains allow B cells to reach splenic compartments even though their B-cell receptors remain autoreactive. Such incompletely edited B cells express multireactive antibodies that accumulate in the Golgi and are released as insoluble, amyloid-like immune complexes. Here, we examine examples of incomplete editing from the analysis of variable to joining (VJ) gene junction of the variable (V?x) editor L chain. When paired with the anti-DNA heavy chain, VH56R, the V?x variants yield antibodies with differing specificities, including glycosaminoglycan reactivity. Our results implicate these specificities in the evasion of receptor editing through intracellular sequestration of IgM and the release of insoluble IgM complexes. Our findings can be extrapolated to human L chains and have implications for understanding a latent component of the Ig repertoire that could exert pathogenic and protective functions.

SUBMITTER: Radic M 

PROVIDER: S-EPMC3718083 | biostudies-other | 2013 Jul

REPOSITORIES: biostudies-other

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Antibodies that bind complex glycosaminoglycans accumulate in the Golgi.

Radic Marko M   Weigert Martin G MG   Khan Salar N SN   Han Jiong J   Kalinina Olga O   Luning Prak Eline T ET  

Proceedings of the National Academy of Sciences of the United States of America 20130701 29

Light (L) chains that edit anti-DNA heavy (H) chains rescue B-cell development by suppressing DNA binding. However, exceptional editor L chains allow B cells to reach splenic compartments even though their B-cell receptors remain autoreactive. Such incompletely edited B cells express multireactive antibodies that accumulate in the Golgi and are released as insoluble, amyloid-like immune complexes. Here, we examine examples of incomplete editing from the analysis of variable to joining (VJ) gene  ...[more]