First Author | Brenner S | Year | 2011 |
Journal | EMBO J | Volume | 30 |
Issue | 13 | Pages | 2705-18 |
PubMed ID | 21623346 | Mgi Jnum | J:174233 |
Mgi Id | MGI:5052229 | Doi | 10.1038/emboj.2011.168 |
Citation | Brenner S, et al. (2011) A hypomorphic IgH-chain allele affects development of B-cell subsets and favours receptor editing. EMBO J 30(13):2705-18 |
abstractText | The quality and quantity of BCR signals impact on cell fate decisions of B lymphocytes. Here, we describe novel gene-targeted mice, which in the context of normal VDJ recombination show hypomorphic expression of immunoglobulin mu heavy chain (muHC) mRNA levels and hence lower pre-BCR and BCR levels. Hypomorphic expression of muHC leads to augmented selection processes at all stages of B-cell development, noticeably at the expansion of pre-B cells, the positive selection of immature B lymphocytes in the bone marrow and the selection of the follicular (FO), marginal zone (MZ) and B1 B-lymphocyte compartment in peripheral lymphoid organs. Immature as well as mature FO and MZ B lymphocytes in the peripheral lymphoid organs express lower levels of the receptor for B-cell activating factor (BAFF). In addition, hypomorphic expression of the BCR favours receptor editing. Together, our results highlight the critical importance of pre-BCR and BCR receptor levels for the normal development of B-lymphocyte subpopulations in the context of intact VDJ recombination and a diverse antibody repertoire. |