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
Language
- eng
Conference Location
- Netherlands