Normal Histology of the Lymphoid Tissues

Lymphoid tissue is found all over the body. It occurs in wellorganized lymphoid organs, such as the lymph nodes and the spleen, or as extranodal lymphoid tissue as part of the gut, skin, and lung. It may develop in any part of the body under specific conditions. The lymphoid organs are divided into central and peripheral organs. The bone marrow and the thymus constitute the central lymphoid organs, and the lymph nodes, the spleen, and extranodal lymphoid tissues constitute the peripheral lymphoid organs. The bone marrow is the site of lymphopoiesis. Some lymphocytic precursors develop into B cells, but most become T cells. The generation of a diversity of effector B cells requires a two-step maturation process. The first step occurs in the bone marrow and results in the development of virgin or naive B cells. The second step takes place in the peripheral lymphoid organs, where affinity maturation of the naive B cells takes place on encounter with a specific antigen, resulting in the formation of plasma cells and memory B cells. The generation of mature T cells occurs exclusively in the thymus, where T-cell precursors develop into a variety of mature CD4-positive (CD4+) and CD8+ T cells through a process of positive and negative selection. T cells do not require further affinity maturation in secondary lymphoid tissues. In contrast to B cells, T cells are activated only in secondary lymphoid organs and start to proliferate on appropriate antigen stimulation. The architecture of the thymus and of the peripheral lymphoid organs offers the ideal microenvironment for these processes. Knowledge of these structures and the immunophenotype of their cellular components within their natural microanatomic environment has improved significantly by the addition of immunohistochemistry to the morphologic studies on lymphoid tissues. Immunophenotyping allows identification of cell lineage and provides information on the stage of maturation, activation, and differentiation of lymphocytes. Immunohistochemistry has offered the opportunity to identify and distinguish more precisely the nonlymphoid components of the lymphoid tissues as well, including the monocyte-derived antigen-presenting cells and macrophages. The use of antibodies against adhesion molecules expressed by endothelial lining cells and by lymphocytes has led to a better understanding of lymphocyte trafficking and homing. Molecular techniques performed on tissue fragments and particularly experiments carried out on selected and defined areas, cell clusters, or on single cells dissected from tissue sections, together with in vitro experiments, and the development of knockout and transgenic animal’s experiments have profoundly changed our understanding of the structure of lymphoid tissues and have resulted in new views and concepts of the functional microanatomy of these tissues as the morphologic substrate of the immune response. This knowledge is essential in the analysis of lymphoid tissues in pathologic conditions, because it is helpful to recognize underlying pathogenic mechanisms. This chapter discusses the histology and the immunohistology of the thymus, lymph node, and spleen and finally factors governing lymphocyte trafficking. The historical description of the microanatomy of these organs, as reported by classic histology, is presented first. This information is complemented by the results obtained by immunohistochemical analysis. The functional significance of the various compartments identified by morphology is discussed. The bone marrow, which is the site of lymphopoiesis in postnatal life and represents an additional microenvironment for B-cell maturation, is discussed in Chapter 1. Particular features of extranodal lymphoid tissues are the subject of Chapter 28.