First Author | Miosge LA | Year | 2002 |
Journal | J Exp Med | Volume | 196 |
Issue | 8 | Pages | 1113-9 |
PubMed ID | 12391023 | Mgi Jnum | J:79725 |
Mgi Id | MGI:2388850 | Doi | 10.1084/jem.20020959 |
Citation | Miosge LA, et al. (2002) Analysis of an Ethylnitrosourea-generated Mouse Mutation Defines a Cell Intrinsic Role of Nuclear Factor kappaB2 in Regulating Circulating B Cell Numbers. J Exp Med 196(8):1113-9 |
abstractText | The number of circulating follicular B lymphocytes is normally kept within a precise range despite their dispersion through the body and daily overproduction of precursors in the bone marrow. By establishing a genome wide recessive mutation screen in C57BL/6 mice to identify critical components of immune system regulation, we identified a mutant strain with selective deficiency in recirculating B cells but not immature or peritoneal B1 cells. Analysis of mixed bone marrow chimeras established that the mutation affects a cell autonomous process within B cells that is required for their accumulation after emigrating to peripheral lymphoid organs. The defect is caused by a point mutation in the gene encoding transcription factor nuclear factor (NF)-kappaB2, terminating the encoded protein within the DNA-binding domain. These findings establish the feasibility of analyzing immune regulation by genome wide mutant screens and demonstrates an intrinsic requirement for NF-kappaB2 in regulating circulating follicular B cell numbers. |