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Publication : Analysis of an ethylnitrosourea-generated mouse mutation defines a cell intrinsic role of nuclear factor kappaB2 in regulating circulating B cell numbers.

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.
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