| First Author | Maki K | Year | 2000 |
| Journal | J Exp Med | Volume | 191 |
| Issue | 8 | Pages | 1333-40 |
| PubMed ID | 10770800 | Mgi Jnum | J:120553 |
| Mgi Id | MGI:3706756 | Doi | 10.1084/jem.191.8.1333 |
| Citation | Maki K, et al. (2000) Immunoglobulin beta signaling regulates locus accessibility for ordered immunoglobulin gene rearrangements. J Exp Med 191(8):1333-40 |
| abstractText | The antigen receptor gene rearrangement at a given locus is tightly regulated with respect to cell lineage and developmental stage by an ill-defined mechanism. To study the possible role of precursor B cell antigen receptor (pre-BCR) signaling in the regulation of the ordered immunoglobulin (Ig) gene rearrangement during B cell differentiation, a newly developed system using mu heavy (H) chain membrane exon (microm)-deficient mice was employed. In this system, the antibody-mediated cross-linking of Igbeta on developmentally arrested progenitor B (pro-B) cells mimicked pre-BCR signaling to induce early B cell differentiation in vivo. Analyses with ligation-mediated polymerase chain reaction revealed that the Igbeta cross-linking induced the redirection of Ig gene rearrangements, namely, the suppression of ongoing rearrangements at the H chain locus and the activation of rearrangements at the light (L) chain locus. Upon the cross-linking, the kappaL chain germline transcription was found to be upregulated whereas the V(H) germline transcription was promptly downregulated. Notably, this alteration of the accessibility at the H and L chain loci was detected even before the induction of cellular differentiation became detectable by the change of surface phenotype. Thus, the pre-BCR signaling through Igbeta appears to regulate the ordered Ig gene rearrangement by altering the Ig locus accessibility. |
