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Publication : A hypomorphic IgH-chain allele affects development of B-cell subsets and favours receptor editing.

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.
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