Kappa editing rescues autoreactive B cells destined for deletion in mice transgenic for a dual specific anti-laminin Ig.

Published

Journal Article

We explored mechanisms involved in B cell self-tolerance in a double- and triple-transgenic mouse model bearing the LamH-C mu Ig H chain conventional transgene and a gene-targeted replacement for a functional V kappa 8J kappa 5 L chain gene. Whereas the H chain is known to generate anti-laminin Ig in combination with multiple L chains, the H + L Ig binds ssDNA in addition to laminin. Immune phenotyping indicates that H + L transgenic B cells are regulated by clonal deletion, receptor editing via secondary rearrangements at the nontargeted kappa allele, and anergy. Collectively, the data suggest that multiple receptor-tolerogen interactions regulate autoreactive cells in the H + L double-transgenic mice. Generation of H + LL triple-transgenic mice homozygous for the targeted L chain to exclude secondary kappa rearrangements resulted in profound B cell depletion with absence of mature B cells in the bone marrow. We propose that the primary tolerogen of dual reactive B cells in this model is not ssDNA, but a strongly cross-linking tolerogen, presumably basement membrane laminin, that triggers recombination-activating gene activity, L chain editing, and deletion.

Full Text

Duke Authors

Cited Authors

  • Brady, GF; Congdon, KL; Clark, AG; Sackey, FNA; Rudolph, EH; Radic, MZ; Foster, MH

Published Date

  • May 1, 2004

Published In

Volume / Issue

  • 172 / 9

Start / End Page

  • 5313 - 5321

PubMed ID

  • 15100270

Pubmed Central ID

  • 15100270

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.172.9.5313

Language

  • eng

Conference Location

  • United States