The perifollicular and marginal zones of the human splenic white pulp - Dofibroblasts guide lymphocyte immigration?

We investigate the white pulp compartments of 73 human spleens and demonstr ate that there are several microanatomical peculiarities in man that do not occur in rats or mice. Humans lack a marginal sinus separating the margina l zone (MZ) from the follicles or the follicular mantle zone. The MZ is div ided into an inner and an outer compartment by a special type of fibroblast s. Ail additional compartment, termed the perifollicular zone, is present b etween the follicular MZ and the red pulp. The perifollicular zone contains sheathed capillaries and blood-filled spaces without endothelial lining. I n the perifollicular zone, in the outer MZ, and in the T cell zone fibrobla sts of an unusual phenotype occur. These cells stain for the adhesion molec ules MAdCAM-1, VCAM-1 (CD106), and VAP-1; the Thy-1 (CD90) molecule; smooth muscle alpha -actin and smooth muscle myosin; cytokeratin 18; and thrombom odulin (CD141). They are, however, negative for the peripheral node address in, the cutaneous lymphocyte antigen, CD34, PECAM-1 (CD31), and P- and E-se lectin (CD62P and CD62E). In the MZ the fibroblasts are often tightly assoc iated with CD4-positive T lymphocytes, whereas CD8-positive cells are almos t absent. our findings lead to the hypothesis, that recirculating CD4-posit ive T lymphocytes enter the human splenic white pulp from the open circulat ion of the perifollicular zone without crossing an endothelium. Specialized fibroblasts may attract these T cells and guide them into the periarteriol ar T cell area.