Antibodies that bind complex glycosaminoglycans accumulate in the Golgi

Marko Radic, Martin G. Weigert, Salar N. Khan, Jiong Han, Olga Kalinina, Eline T.Luning Prak

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 (Vγx) editor L chain. When paired with the anti- DNA heavy chain, V H56R, the Vγx 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.

Original languageEnglish (US)
Pages (from-to)11958-11963
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number29
DOIs
StatePublished - Jul 16 2013

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Glycosaminoglycans
B-Lymphocytes
Antibodies
Immunoglobulin M
DNA
Antigen-Antibody Complex
Amyloid
Light
Genes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Antibodies that bind complex glycosaminoglycans accumulate in the Golgi. / Radic, Marko; Weigert, Martin G.; Khan, Salar N.; Han, Jiong; Kalinina, Olga; Prak, Eline T.Luning.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 29, 16.07.2013, p. 11958-11963.

Research output: Contribution to journalArticle

Radic, Marko ; Weigert, Martin G. ; Khan, Salar N. ; Han, Jiong ; Kalinina, Olga ; Prak, Eline T.Luning. / Antibodies that bind complex glycosaminoglycans accumulate in the Golgi. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 29. pp. 11958-11963.
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