| First Author | Yunk L | Year | 2009 |
| Journal | J Immunol | Volume | 183 |
| Issue | 1 | Pages | 452-61 |
| PubMed ID | 19542457 | Mgi Jnum | J:149969 |
| Mgi Id | MGI:3849494 | Doi | 10.4049/jimmunol.0804060 |
| Citation | Yunk L, et al. (2009) Antibodies in a heavy chain knock-in mouse exhibit characteristics of early heavy chain rearrangement. J Immunol 183(1):452-61 |
| abstractText | Studies in autoantibody transgenic mice have demonstrated receptor editing rearrangements at Ab H and L chain loci. However, the physiologic role of H chain editing (V(H) replacement and rearrangement on the second allele) has been called into question. It is unclear if additional rounds of H chain rearrangement are driven by BCR specificity. In this study, we analyze the manner in which B cells undergo additional H chain rearrangements in an anti-DNA H chain knock-in mouse, B6.56R. We find that rearrangements in 56R(+) B cells tend to involve the D gene locus on both alleles and the most J(H)-proximal V(H) gene segments on the endogenous allele. As a result, some B cells exhibit V(D)J rearrangements on both H chain alleles, yet allelic exclusion is tightly maintained in mature 56R B cells. As B cells mature, a higher proportion expresses the nontransgenic H chain allele. Rearrangements on both H chain alleles exhibit junctional diversity consistent with TdT-mediated N-addition, and TdT RNA is expressed exclusively at the pro-B cell stage in B6.56R. Collectively, these findings favor a single, early window of H chain rearrangement in B6.56R that precedes the expression of a functional BCR. B cells that happen to successfully rearrange another H chain may be favored in the periphery. |
