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Analysis of an Ethylnitrosourea-generated Mouse Mutation Defines a Cell Intrinsic Role of Nuclear Factor κB2 in Regulating Circulating B Cell Numbers

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 i...

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Detalles Bibliográficos
Autores principales: Miosge, Lisa A., Blasioli, Julie, Blery, Mathieu, Goodnow, Christopher C.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194042/
https://www.ncbi.nlm.nih.gov/pubmed/12391023
http://dx.doi.org/10.1084/jem.20020959
Descripción
Sumario: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)-κB2, 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-κB2 in regulating circulating follicular B cell numbers.