Skip to main content
release_alert
Welcome to the new Scholars 3.0! Read about new features and let us know what you think.
cancel
Journal cover image

Diverse endogenous light chains contribute to basement membrane reactivity in nonautoimmune mice transgenic for an anti-laminin Ig heavy chain.

Publication ,  Journal Article
Fitzsimons, MM; Chen, H; Foster, MH
Published in: Immunogenetics
January 2000

Basement membrane proteins are targeted in a variety of pathologic autoimmune responses, yet little is known regarding the origins and regulation of this subset of pathogenic lymphocytes. To examine the generation and fate of B cells reactive with a matrix autoantigen, nonautoimmune C57BL/6 mice were rendered transgenic for a nephrotropic lupus anti-laminin immunoglobulin (Ig) H chain, termed LamH-Cmu. We previously reported recovery of two distinct phenotypes among LamH-Cmu-transgenic mice: progeny of founders M6 and M29 contained abundant transgene-expressing B cells but little anti-laminin Ig, whereas spontaneous autoreactivity was readily recovered from the M7 lineage that expressed minimal B-cell mIgM. To explore the spectrum of autoreactivity generated in vivo by different LamH-Cmu-endogenous L-chain combinations, we determined in vitro and in vivo antigen reactivity and L-chain V-region sequences of 17 LamH-Cmu-transgenic anti-laminin Igs. The results reveal a heterogeneous population of anti-laminin Igs with different fine specificities encoded by diverse endogenous L chains, encompassing nine different Vk gene families, 11 Vk genes, and three Jk genes. Many of the L chains are identical to known or putative unmutated germline Vk genes used to encode Igs reactive with self and foreign antigens in nonautoimmune and genetically autoimmune-prone mouse strains. These observations confirm that the LamH-Cmu H chain plays a dominant role in determining anti-laminin reactivity, and indicate that nonautoimmune B6 mice are fully capable of generating a diverse pool of basement-membrane-reactive B cells using unmutated Ig genes. When interpreted in the context of the divergent M6/M29 and M7 transgenic mouse phenotypes, our findings further suggest that these matrix-reactive lymphocytes are not spontaneously activated in vivo under normal circumstances.

Duke Scholars

Published In

Immunogenetics

DOI

ISSN

0093-7711

Publication Date

January 2000

Volume

51

Issue

1

Start / End Page

20 / 29

Location

United States

Related Subject Headings

  • Transgenes
  • Molecular Sequence Data
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Laminin
  • Kidney
  • Immunology
  • Immunoglobulin mu-Chains
  • Immunoglobulin kappa-Chains
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Fitzsimons, M. M., Chen, H., & Foster, M. H. (2000). Diverse endogenous light chains contribute to basement membrane reactivity in nonautoimmune mice transgenic for an anti-laminin Ig heavy chain. Immunogenetics, 51(1), 20–29. https://doi.org/10.1007/s002510050004
Fitzsimons, M. M., H. Chen, and M. H. Foster. “Diverse endogenous light chains contribute to basement membrane reactivity in nonautoimmune mice transgenic for an anti-laminin Ig heavy chain.Immunogenetics 51, no. 1 (January 2000): 20–29. https://doi.org/10.1007/s002510050004.
Fitzsimons, M. M., et al. “Diverse endogenous light chains contribute to basement membrane reactivity in nonautoimmune mice transgenic for an anti-laminin Ig heavy chain.Immunogenetics, vol. 51, no. 1, Jan. 2000, pp. 20–29. Pubmed, doi:10.1007/s002510050004.
Journal cover image

Published In

Immunogenetics

DOI

ISSN

0093-7711

Publication Date

January 2000

Volume

51

Issue

1

Start / End Page

20 / 29

Location

United States

Related Subject Headings

  • Transgenes
  • Molecular Sequence Data
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Laminin
  • Kidney
  • Immunology
  • Immunoglobulin mu-Chains
  • Immunoglobulin kappa-Chains