| First Author | Muljo SA | Year | 2002 |
| Journal | Int Immunol | Volume | 14 |
| Issue | 6 | Pages | 577-84 |
| PubMed ID | 12039909 | Mgi Jnum | J:77058 |
| Mgi Id | MGI:2180953 | Doi | 10.1093/intimm/dxf023 |
| Citation | Muljo SA, et al. (2002) The variable, C(H)1, C(H)2 and C(H)3 domains of Ig heavy chain are dispensable for pre-BCR function in transgenic mice. Int Immunol 14(6):577-84 |
| abstractText | The pre-BCR consists of Ig micro protein, the product of a heavy chain gene assembled by V(D)J recombination in pro-B cells, the surrogate light chains V(pre-B) and lambda 5, and the signaling chains Ig alpha and Ig beta. Signaling by the pre-BCR is a checkpoint required for further maturation of pro-B cells in the adult bone marrow. However, it is currently not known whether an extracellular ligand is required to initiate pre-BCR signaling. We reasoned that if the ectodomain of the pre-BCR is required to interact with a ligand, then a truncated heavy chain protein would not support B cell development. To test this notion, we produced transgenic mice expressing a heavy chain protein whose extracellular domains except for C(H)4 were replaced by an irrelevant Ig superfamily ectodomain from the human CD8 alpha protein. This transgene resulted in pre-BCR-like signaling since it rescued development of pre-B cells in recombinase-activating gene (RAG)1-deficient mice and resulted in allelic exclusion of the endogenous Ig heavy chain gene in RAG-proficient mice. These findings lead us to suggest that the majority of the extracellular region of the pre-BCR is not required for pre-BCR function and, thus, ligand binding is unlikely to be required for pre-BCR function. |
