Genetic elimination of α3(IV) collagen fails to rescue anti-collagen B cells.

Journal Article (Journal Article)

Organ deposition of autoantibodies against the noncollagenous-1 domain of the α3 chain of type IV collagen leads to severe kidney and lung injury in anti-glomerular basement membrane disease. The origin and regulation of these highly pathogenic autoantibodies remains unknown. Anti-α3(IV) collagen B lymphocytes are predicted to mature in vivo ignorant of target antigen because α3(IV) collagen expression is highly tissue restricted and pathogenic epitopes are cryptic. However, a recent analysis of an anti-α3(IV)NC1 collagen autoantibody transgenic mouse model revealed that developing B cells are rapidly silenced by deletion and editing in the bone marrow. To dissect the role of collagen as central tolerogen in this model, we determined B cell fate in autoantibody transgenic mice genetically lacking α3(IV) collagen. We found that absence of the tissue target autoantigen has little impact on the fate of anti-α3(IV)NC1 B cells. This implies a more complex regulatory mechanism for preventing anti-glomerular basement membrane disease than has been previously considered, including the possibility that a second antigen present in bone marrow engages and tolerizes anti-α3(IV)NC1 collagen B cells.

Full Text

Duke Authors

Cited Authors

  • Clark, AG; Mackin, KM; Foster, MH

Published Date

  • December 30, 2011

Published In

Volume / Issue

  • 141 / 1

Start / End Page

  • 134 - 139

PubMed ID

  • 21963654

Pubmed Central ID

  • PMC3260941

Electronic International Standard Serial Number (EISSN)

  • 1879-0542

Digital Object Identifier (DOI)

  • 10.1016/j.imlet.2011.09.004


  • eng

Conference Location

  • Netherlands