Genetic elimination of α3(IV) collagen fails to rescue anti-collagen B cells.
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.
Duke Scholars
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Related Subject Headings
- Self Tolerance
- Models, Animal
- Mice, Transgenic
- Mice, Inbred C57BL
- Mice, Inbred BALB C
- Mice
- Immunology
- Extracellular Matrix
- Epitopes
- Disease Models, Animal
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Self Tolerance
- Models, Animal
- Mice, Transgenic
- Mice, Inbred C57BL
- Mice, Inbred BALB C
- Mice
- Immunology
- Extracellular Matrix
- Epitopes
- Disease Models, Animal