The Perifollicular and Marginal Zones of the Human Splenic White Pulp

Abstract

We investigate the white pulp compartments of 73 human spleens and demonstrate that there are several microanatomical peculiarities in man that do not occur in rats or mice. Humans lack a marginal sinus separating the marginal zone (MZ) from the follicles or the follicular mantle zone. The MZ is divided into an inner and an outer compartment by a special type of fibroblasts. An additional compartment, termed the perifollicular zone, is present between the follicular MZ and the red pulp. The perifollicular zone contains sheathed capillaries and blood-filled spaces without endothelial lining. In the perifollicular zone, in the outer MZ, and in the T cell zone fibroblasts of an unusual phenotype occur. These cells stain for the adhesion molecules MAdCAM-1, VCAM-1 (CD106), and VAP-1; the Thy-1 (CD90) molecule; smooth muscle alpha-actin and smooth muscle myosin; cytokeratin 18; and thrombomodulin (CD141). They are, however, negative for the peripheral node addressin, the cutaneous lymphocyte antigen, CD34, PECAM-1 (CD31), and P- and E-selectin (CD62P and CD62E). In the MZ the fibroblasts are often tightly associated with CD4-positive T lymphocytes, whereas CD8-positive cells are almost absent. Our findings lead to the hypothesis, that recirculating CD4-positive T lymphocytes enter the human splenic white pulp from the open circulation of the perifollicular zone without crossing an endothelium. Specialized fibroblasts may attract these T cells and guide them into the periarteriolar T cell area.

CCL21 Expression Pattern of Human Secondary Lymphoid Organ Stroma Is Conserved in Inflammatory Lesions with Lymphoid Neogenesis

“…40,50 Further studies have shown that murine FRCs also express CCL19, 15 ERTR7, 51 desmin, and SMA, 40 a reliable marker of myofibroblasts. 42 Although the specific features of this apparatus in human SLOs have been less extensively investigated, 39,52 our observations strongly indicate that CD45 Ϫ , CCL21 ϩ , SMA ϩ fibroblastoid cells, which we have identified in human SLOs, represent FRCs as suggested by their phenotypic marker expression, their dendroid morphology, and their reticular distribution throughout the T area and among the subcapsular sinus and HEVs. The inability to detect CCL21 expression in human SLO SMA ϩ fibroblast cell lines in basal conditions or on in vitro stimulation with tumor necrosis factor-␣ and lymphotoxin, which have been shown to be required for normal expression of CCL21 in mouse spleen, 53 is in keeping with previous reports in murine LN FRCs.…”

The Actin-binding Protein Caldesmon Is in Spleen and Lymph Nodes Predominately Expressed by Smooth-muscle Cells, Reticular Cells, and Follicular Dendritic Cells

“…The reticular network must permit great volume changes during an immune response, e.g., associated with the development and regression of germinal centers (Veerman and Vries 1976;Liu et al 1991;Hollowood and Macartney 1992). Accordingly, contractile proteins characteristic of smooth muscle are expressed by reticular cells (Pinkus et al 1986;Toccanier-Pelte et al 1987;Satoh et al 1997Satoh et al ,2009Steiniger et al 2001).…”

<b>Three-dimensional reconstruction of serial sections for analysis of the microvasculature of the white pulp and the marginal zone in the human </b><b>spleen </b>

“…SEM of vascular corrosion casts of the human spleen (7) has further confirmed that some of the penicillar arteries, after passing through a splenic follicle, make a hairpin turn and return to the follicle to form bundler arteries. Immunohistochemical studies have focused on the vasculature of the human spleen (11)(12)(13)(14)(15)(16)(17)(18)(19). Steiniger et al performed double staining of serial sections of human spleens for CD34 (a marker for the vascular endothelium) and CD141 (a marker for the sinus en-oxidase activity.…”