Analysis of an ethylnitrosourea-generated mouse mutation defines a cell intrinsic role of nuclear factor kappaB2 in regulating circulating B cell numbers
| Autor: | Christopher C. Goodnow, Lisa A. Miosge, Julie Blasioli, Mathieu Blery |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
Immunology Mutant Molecular Sequence Data Rel/NF-κB Biology Chimera (genetics) Mice ethylnitrosourea NF-kappa B p52 Subunit follicular medicine Immunology and Allergy Animals Point Mutation Follicular B cell Amino Acid Sequence Transcription factor B cell B-Lymphocytes NF-kappa B Brief Definitive Report NFKB1 Molecular biology Immunohistochemistry B-1 cell Mice Inbred C57BL medicine.anatomical_structure Female Bone marrow mutagenesis B lymphocytes |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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