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

Publication ,  Journal Article
Clark, AG; Mackin, KM; Foster, MH
Published in: Immunol Lett
December 30, 2011

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

Published In

Immunol Lett

DOI

EISSN

1879-0542

Publication Date

December 30, 2011

Volume

141

Issue

1

Start / End Page

134 / 139

Location

Netherlands

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

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MLA
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Clark, A. G., Mackin, K. M., & Foster, M. H. (2011). Genetic elimination of α3(IV) collagen fails to rescue anti-collagen B cells. Immunol Lett, 141(1), 134–139. https://doi.org/10.1016/j.imlet.2011.09.004
Clark, Amy G., Katherine M. Mackin, and Mary H. Foster. “Genetic elimination of α3(IV) collagen fails to rescue anti-collagen B cells.Immunol Lett 141, no. 1 (December 30, 2011): 134–39. https://doi.org/10.1016/j.imlet.2011.09.004.
Clark AG, Mackin KM, Foster MH. Genetic elimination of α3(IV) collagen fails to rescue anti-collagen B cells. Immunol Lett. 2011 Dec 30;141(1):134–9.
Clark, Amy G., et al. “Genetic elimination of α3(IV) collagen fails to rescue anti-collagen B cells.Immunol Lett, vol. 141, no. 1, Dec. 2011, pp. 134–39. Pubmed, doi:10.1016/j.imlet.2011.09.004.
Clark AG, Mackin KM, Foster MH. Genetic elimination of α3(IV) collagen fails to rescue anti-collagen B cells. Immunol Lett. 2011 Dec 30;141(1):134–139.
Journal cover image

Published In

Immunol Lett

DOI

EISSN

1879-0542

Publication Date

December 30, 2011

Volume

141

Issue

1

Start / End Page

134 / 139

Location

Netherlands

Related Subject Headings

  • Self Tolerance
  • Models, Animal
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Immunology
  • Extracellular Matrix
  • Epitopes
  • Disease Models, Animal