Differential expression of IRF8 in subsets of macrophages and dendritic cells and effects of IRF8 deficiency on splenic B cell and macrophage compartments - PubMed (original) (raw)

Differential expression of IRF8 in subsets of macrophages and dendritic cells and effects of IRF8 deficiency on splenic B cell and macrophage compartments

Chen-Feng Qi et al. Immunol Res. 2009.

Abstract

IRF8, a transcription factor restricted primarily to hematopoietic cells, is known to influence the differentiation and function of dendritic cells (DC), macrophages, granulocytes and B cells. In human tonsil, IRF8 is expressed at high levels by intrafollicular macrophages and DC, but at much lower levels by tingible body macrophages in germinal centers (GCs) and little, if at all, by follicular DC. Spleens of IRF8-deficient mice had reduced numbers of white pulp follicles and GCs that were irregular in shape. The frequency of follicular B cells was significantly reduced while the population of marginal zone (MZ) B cells was increased. In addition, MZ macrophages were reduced in number and abnormally distributed, while metallophilic macrophages were normal. These findings demonstrate differential requirements for IRF8 among distinct subsets of B cells, DC, and macrophages.

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Figures

Fig. 1

Fig. 1

Anti-IRF8 IHC staining of Human tonsil samples. Large arrows show tangible body macrophages, small arrows show FDCs

Fig. 2

Fig. 2

Confocal microscopic analyses of GCs from IRF8+/+(+/+) and IRF8−/− (−/−) spleens for expression of BCL6 and FDC-M1. The merged images are shown at the bottom

Fig. 3

Fig. 3

H&E staining of spleens from IRF8+/+(+/+) and IRF8−/− (−/−) mice. Original magnifications are indicated to the left. Germinal centers are circled in the lower four panels and arrows point to apoptotic bodies localized outside germinal centers

Fig. 4

Fig. 4

Confocal microscopic analyses of normal spleen co-stained with antibodies to anti-IRF8 and FDC-M1. The merged images are shown at the bottom

Fig. 5

Fig. 5

FASC analyses of spleen cells from IRF8+/+(+/+) and IRF8−/− (−/−) mice. The left panels, gated to show lymphocytes, show results obtained with antibodies to IgM and B220 and the gates used for characterization of B cells for expression of CD21 and CD23 shown in the right panels. Numbers in the right panel indicate the percentages of total B cells. In the right panels, the gates for follicular (FO) B cells (CD23hiCD21lo) and marginal zone (MZ) B cells (CD23lo/−CD21hi) are indicated together with the percentages of cells falling in the gates. Data are representative of five or more independent experiments

Fig. 6

Fig. 6

Confocal microscopic analyses of GCs from IRF8+/+(+/+) and IRF8−/− (−/−) spleens for expression of the indicated pairs of cell surface markers

Fig. 7

Fig. 7

Confocal microscopic studies of GCs from IRF8+/+(+/+) and IRF8−/− (−/−) mice for expression of ERTR-9 on MZ macrophages, MOMA-1 on metallophilic macrophages, and MadCAM-1 on marginal sinus endothelial cells and activated FDCs

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References

    1. Cozine CL, Wolniak KL, Waldschmidt TJ. The primary germinal center response in mice. Curr Opin Immunol. 2005;17:298–302. - PubMed
    1. Martin F, Kearney JF. Marginal-zone B cells. Nat Rev Immunol. 2002;2:323–35. - PubMed
    1. Mebius RE, Nolte MA, Kraal G. Development and function of the splenic marginal zone. Crit Rev Immunol. 2004;24:449–64. - PubMed
    1. Schwickert TA, Lindquist RL, Shakhar G, Livshits G, Skokos D, Kosco-Vilbois MH, et al. In vivo imaging of germinal centres reveals a dynamic open structure. Nature. 2007;446:83–7. - PubMed
    1. Allen CD, Okada T, Tang HL, Cyster JG. Imaging of germinal center selection events during affinity maturation. Science. 2007;315:528–31. - PubMed

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