First Author | Yachimovich N | Year | 2002 |
Journal | Eur J Immunol | Volume | 32 |
Issue | 4 | Pages | 1164-74 |
PubMed ID | 11932924 | Mgi Jnum | J:75975 |
Mgi Id | MGI:2178170 | Doi | 10.1002/1521-4141(200204)32:4<1164::AID-IMMU1164>3.0.CO;2-1 |
Citation | Yachimovich N, et al. (2002) The efficiency of B cell receptor (BCR) editing is dependent on BCR light chain rearrangement status. Eur J Immunol 32(4):1164-74 |
abstractText | Anti-DNA knock-in mice serve as models for studying B cell tolerance mechanisms to a ubiquitous antigen. We have constructed six strains of double transgenic (C57BL/6xBALB/c)F1 mice, eachexpressing an unmutated or somatically mutated anti-DNA heavy (H) chain, combined with one of three different light (L) chains, namely V(kappa)1-J(kappa)1, V(kappa)4-J(kappa)4 and V(kappa)8-J(kappa)5. In vitro analysis of the various Ig H/L chain combinations showed that all had a similar specificity for single-stranded DNA and double-stranded DNA, but that antibodies encoded by the mutated H chain had higher affinities for the autoantigen. None of the targeted mouse strains exhibited significant levels of serum anti-DNA activity. However, while B cells from mice carrying the V(kappa)1-J(kappa)1 transgenic L chains were tolerized almost exclusively by L chain receptor editing in an affinity-independent manner, the mice expressing V(kappa)8-J(kappa)5 L chains have utilized affinity-dependent clonal anergy as their sole mechanism of B cell tolerance. V(kappa)4-J(kappa)4 targeted mice exhibited an intermediate phenotype with respect to these two mechanisms of B cell tolerance. Our results suggest that receptor editing is the preferred mechanism of B cell tolerance and that the efficiency of L chain editing is directly related to the number of available J(kappa) segments on the expressed V(kappa) allele. |