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Transcription factor IRF4 regulates germinal center cell formation through a B cell-intrinsic mechanism.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2014 Apr 01; Vol. 192 (7), pp. 3200-6. Date of Electronic Publication: 2014 Mar 03. - Publication Year :
- 2014
-
Abstract
- In response to antigenic stimulation, mature B cells interact with follicular helper T cells in specialized structures called germinal centers (GCs), which leads to the development of memory B cells and Ab-secreting plasma cells. The transcription factor IFN regulatory factor 4 (IRF4) is essential for the formation of follicular helper T cells and thus GCs, although whether IRF4 plays a distinct role in GC B cells remains contentious. RNAseq analysis on ex vivo-derived mouse B cell populations showed that Irf4 was lowly expressed in naive B cells, highly expressed in plasma cells, but absent from GC B cells. In this study, we used conditional deletion of Irf4 in mature B cells as well as wild-type and Irf4-deficient mixed bone marrow chimeric mice to investigate how and where IRF4 plays its essential role in GC formation. Strikingly, GC formation was severely impaired in mice in which Irf4 was conditionally deleted in mature B cells, after immunization with protein Ags or infection with Leishmania major. This effect was evident as early as day 5 following immunization, before the development of GCs, indicating that Irf4 was required for the development of early GC B cells. This defect was B cell intrinsic because Irf4-deficient B cells in chimeric mice failed to participate in the GC in response to L. major or influenza virus infection. Taken together, these data demonstrate a B cell-intrinsic requirement for IRF4 for not only the development of Ab secreting plasma cells but also for GC formation.
- Subjects :
- Animals
Antigens immunology
B-Lymphocytes metabolism
Cell Differentiation genetics
Cell Differentiation immunology
Flow Cytometry
Gene Expression immunology
Germinal Center cytology
Germinal Center metabolism
Host-Pathogen Interactions immunology
Influenza A Virus, H3N2 Subtype immunology
Influenza A Virus, H3N2 Subtype physiology
Interferon Regulatory Factors genetics
Interferon Regulatory Factors metabolism
Leishmania major immunology
Leishmania major physiology
Leishmaniasis, Cutaneous genetics
Leishmaniasis, Cutaneous immunology
Leishmaniasis, Cutaneous microbiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Orthomyxoviridae Infections genetics
Orthomyxoviridae Infections immunology
Orthomyxoviridae Infections virology
Plasma Cells metabolism
Receptors, IgE genetics
Receptors, IgE immunology
Receptors, IgE metabolism
Sequence Analysis, RNA methods
T-Lymphocytes, Helper-Inducer metabolism
B-Lymphocytes immunology
Germinal Center immunology
Interferon Regulatory Factors immunology
Plasma Cells immunology
T-Lymphocytes, Helper-Inducer immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 192
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 24591370
- Full Text :
- https://doi.org/10.4049/jimmunol.1303216