| First Author | Corcoran AE | Year | 1998 |
| Journal | Nature | Volume | 391 |
| Issue | 6670 | Pages | 904-7 |
| PubMed ID | 9495344 | Mgi Jnum | J:46133 |
| Mgi Id | MGI:1197172 | Doi | 10.1038/36122 |
| Citation | Corcoran AE, et al. (1998) Impaired immunoglobulin gene rearrangement in mice lacking the IL-7 receptor. Nature 391(6670):904-7 |
| abstractText | To generate the full diversity of antibody heavy-chain genes, hundreds of dispersed germline V segments must undergo recombination following D-J segment joining. Here we report that this process is regulated by the alpha- chain of the receptor for interleukin-7, a cytokine that stimulates B-cell lymphopoiesis(1). D-J joining occurs normally in immature B lymphocytes from mice lacking the alpha-chain of the interleukin-7 receptor (IL-7R alpha). But recombination of V segments is progressively impaired as their distance increases upstream of D/J, causing infrequent rearrangement of most V segments, which markedly reduces diversity. This is not simply due to defective cell proliferation or impaired recombinase expression. Rather, germline transcripts from distal, unrearranged V segments, a marker of chromatin changes that precede recombination, are specifically silenced. So too is expression of Pax-5, which binds to heavy-chain locus control elements and normally stimulates recombination, suggesting a mechanism for these effects. Thus ligands of the interleukin-7 receptor deliver an extrinsic signal that targets. V segment recombination in the heavy-chain locus by altering the accessibility of DNA substrates to the recombinase. This mechanism augments the recombinational diversity of the primary antibody repertoire. |
