Embryologic, Histologic, and Anatomic Aspects
Langerhans’ cells, named for Paul Langerhans who, while a medical student in Berlin in 1868, was the first to describe them, are dendritic cells that reside just above the middle of the spinous zone of the epidermis. They make their appearance there by the 14th week of fetal life. From their origin in the bone marrow, Langerhans” cells proceed to populate the epidermis, dermis, thymus, tonsils, lymph nodes, and epithelia of the oral and genital mucous membranes. Within the epidermis, they replicate, the estimated time for completion of their cycle being 16 days. Although Langerhans” cells represent about 4% of the entire population of cells in the epidermis, the distribution of them varies according to anatomic site, the range being between 460 and 1,000 per mm2 of epidermis. Fine unmyelinated nerve fibers ascend into the epidermis where they seem to touch Langerhans” cells, thereby creating a link between the nervous and immune systems. Nerves, by virtue of release from them of neuropeptides, such as calcitonin gene-related peptide, are able to modulate the function of Langerhans”cells.
In sections stained by hematoxylin and eosin, Langerhans” cells are seen to be separated from adjacent keratocytes by a cleft, just as melanocytes are separated from keratocytes by a space, a finding that for more than a century caused them to be interpreted incorrectly as “high-level melanocytes.” In fact, the space that surrounds Langerhans” cells is an artifact caused by shrinkage during processing, just as is the case for melanocytes. The most reliable means for identification of Langerhans” cells is electron microscopy, which reveals within the cytoplasm of them characteristic granules that display a hemispherical bleb at one end of a linear platelike structure. The appearance in vertical section of these Birbeck granules has been likened to that of a tennis racquet (Fig. 1.68). Cells identical in all respects to Langerhans” cells, except for lack of Birbeck’s granules, have been termed indeterminate cells. A calcium-dependent lectin with specificity for binding mannose, namely, langerin, is thought to induce formation of Birbeck’s granules.
Langerhans” granules display a tennis-racket configuration that results from dilation at one end of the organelle. (x82,600) (Courtesy of Alvin Zelickson, M.D.)
Langerhans” cells are similar to macrophages and, like them, possess cell surface HLADR, which is necessary for presentation of antigen to lymphocytes, and membrane receptors for both the C3b component of complement and the Fc portion of IgG and IgE. Those markers are important for recognition of antigens and presentation of antigens to T lymphocytes, functions that make Langerhans” cells instrumental in the development of allergic contact sensitivity. Langerhans” cells express CD1a and S100 antigens that permit them to be recognized by immunohistochemical techniques.
In sum, the Langerhans” cell is distinctive morphologically and plays a crucial role in various immune processes, among them allergic contact dermatitis, allograft rejection, immune tolerance, and surveillance for incipient neoplasia.