Genetic elimination of alpha 3(IV) collagen fails to rescue anti-collagen B cells

Organ deposition of autoantibodies against the noncollagenous-1 domain of the alpha 3 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- alpha 3(IV)...

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Bibliographic Details
Published in:Immunology letters 2011-12, Vol.141 (1), p.134-139
Main Authors: Clark, Amy G, Mackin, Katherine M, Foster, Mary H
Format: Article
Language:English
Subjects:
Animal models
Autoantibodies
Autoantigens
Basement membranes
Bone marrow
Cell fate
Collagen (type IV)
Epitopes
Injuries
Kidney
Lymphocytes B
Transgenic mice
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Summary:Organ deposition of autoantibodies against the noncollagenous-1 domain of the alpha 3 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- alpha 3(IV) collagen B lymphocytes are predicted to mature in vivo ignorant of target antigen because alpha 3(IV) collagen expression is highly tissue restricted and pathogenic epitopes are cryptic. However, a recent analysis of an anti- alpha 3(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 alpha 3(IV) collagen. We found that absence of the tissue target autoantigen has little impact on the fate of anti- alpha 3(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- alpha 3(IV)NC1 collagen B cells.
ISSN:0165-2478
DOI:10.1016/j.imlet.2011.09.004