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.
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21 October 2002
Brief Definitive Report|
October 21 2002
Analysis of an Ethylnitrosourea-generated Mouse Mutation Defines a Cell Intrinsic Role of Nuclear Factor κB2 in Regulating Circulating B Cell Numbers
Lisa A. Miosge,
Lisa A. Miosge
Australian Cancer Research Foundation Genetics Laboratory and Medical Genome Centre, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia
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Julie Blasioli,
Julie Blasioli
Australian Cancer Research Foundation Genetics Laboratory and Medical Genome Centre, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia
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Mathieu Blery,
Mathieu Blery
Australian Cancer Research Foundation Genetics Laboratory and Medical Genome Centre, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia
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Christopher C. Goodnow
Christopher C. Goodnow
Australian Cancer Research Foundation Genetics Laboratory and Medical Genome Centre, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia
Search for other works by this author on:
Lisa A. Miosge
Australian Cancer Research Foundation Genetics Laboratory and Medical Genome Centre, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia
Julie Blasioli
Australian Cancer Research Foundation Genetics Laboratory and Medical Genome Centre, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia
Mathieu Blery
Australian Cancer Research Foundation Genetics Laboratory and Medical Genome Centre, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia
Christopher C. Goodnow
Australian Cancer Research Foundation Genetics Laboratory and Medical Genome Centre, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia
Address correspondence to Christopher C. Goodnow, Australian Cancer Research Foundation Genetics Laboratory, Medical Genome Centre, John Curtin School of Medical Research, Mills Rd., PO Box 334, Australian National University, Canberra ACT 2601, Australia. Phone: 61-2-6125-3621; Fax: 61-2-6125-8512; E-mail: [email protected]
Received:
June 12 2002
Revision Received:
August 19 2002
Accepted:
September 16 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2002
J Exp Med (2002) 196 (8): 1113–1119.
Article history
Received:
June 12 2002
Revision Received:
August 19 2002
Accepted:
September 16 2002
Citation
Lisa A. Miosge, Julie Blasioli, Mathieu Blery, Christopher C. Goodnow; Analysis of an Ethylnitrosourea-generated Mouse Mutation Defines a Cell Intrinsic Role of Nuclear Factor κB2 in Regulating Circulating B Cell Numbers . J Exp Med 21 October 2002; 196 (8): 1113–1119. doi: https://doi.org/10.1084/jem.20020959
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