Restricted expression of E2A protein in primary human tissues correlates with proliferation and differentiation - PubMed (original) (raw)

Restricted expression of E2A protein in primary human tissues correlates with proliferation and differentiation

M N Rutherford et al. Am J Pathol. 1998 Jul.

Abstract

E2A is a basic helix-loop-helix (bHLH) transcription factor required for B cell lymphopoiesis and implicated in myogenesis and the regulation of insulin expression. As E2A is expressed widely in tissues, tissue-specific downstream effects are thought to result primarily from dimerization with other bHLH proteins. To investigate the degree to which regulation of E2A protein abundance may serve to regulate E2A function, expression of E2A was evaluated using immunohistochemistry on histological sections of primary human tissues. Somewhat surprisingly, nuclear staining for E2A was restricted in all tissues examined, often to a small subpopulation of cells. In some tissues, such as adult liver, expression was absent or limited to rare infiltrating lymphocytes. E2A-expressing cells were most abundant in lymphoid tissues. In tonsil, lymph node, and spleen, expression appeared most abundant and prevalent among rapidly proliferating centroblasts of the germinal center dark zone. Scattered E2A-expressing thymocytes were more numerous in the thymic cortex than medulla. In developing skeletal muscle, E2A was detectable in striated myotubes but not in more primitive mononucleated progenitors or mature muscle. Differential E2A expression was also noted in proliferating periventricular neuroepithelial cells in the developing brain. These results suggest that regulation of E2A abundance complements protein-protein interactions in modulating E2A function.

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Figures

Figure 1.

Figure 1.

E2A expression in hyperplastic tonsil. A: E2A-expressing cells are most prevalent within the germinal centers of secondary lymphoid follicles. B: On higher magnification, immunoreactive cells are concentrated in the basal region of the germinal center, furthest from the broadest portion of the mantle zone (MZ), in an area corresponding to the dark zone. Staining is clearly nuclear (inset).

Figure 2.

Figure 2.

Distribution of E2A-expressing cells correlated with germinal center subcompartments. In consecutive histological sections of frozen tonsil tissue, the basal region of the germinal center containing the greatest number of E2A-immunoreactive cells corresponds to the dark zone (DZ), as defined by maximal expression of Ki-67, indicating proliferative cells. Follicular dendritic cells expressing CD23 are most numerous in the apical light zone (LZ) and appear absent from the dark zone.

Figure 3.

Figure 3.

Co-localization of E2A with the proliferation marker Ki-67 in a lymphoid follicle. Cells expressing E2A (green) have a similar distribution to those expressing Ki-67 (red) when the two proteins are detected in the same histological section of frozen tonsil tissue. Digital superimposition of the two images causes co-expressing cells to appear as yellow or pale orange. This indicates that the overwhelming majority of E2A-expressing cells in the dark zone (centroblasts) are in cycle.

Figure 4.

Figure 4.

Distribution of E2A-expressing cells in juvenile thymus. Scattered immunoreactive cells appear somewhat more numerous in the cortex (C) than in the medulla (M).

Figure 5.

Figure 5.

E2A expression in fetal (Carnegie stage 22) spinal cord and muscle. In the spinal cord, partial overlap is observed between cells expressing E2A and the proliferation marker Ki-67. However, whereas E2A expression appears most abundant in the subventricular zone, Ki-67 is most prevalently expressed in the ventricular zone (VZ), immediately subjacent to the spinal canal. In developing muscle, nuclear staining for E2A is restricted to the more differentiated, multinucleated myotubes. In contrast, expression of Ki-67 is not detectable in myotubes but prominent in mononuclear myoblasts.

Figure 6.

Figure 6.

E2A expression in fetal (Carnegie stage 23) kidney and testis. A: In the kidney, the most intense staining is in glomeruli at various stages of development, although more primitive epithelioid elements and interstitial mesenchymal cells are also stained. B: In the testis, expression is detectable in germ cells within seminiferous tubules and in scattered interstitial cells.

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