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INTRODUCTION

Normal lymphopoiesis is an essential component in host defense. It involves the proliferation and function of several types of lymphoid cells including B cells, which are the antibody-producing cells; T cells, which carry out cell-mediated immune functions and are largely responsible for regulatory control of the immune system; and the natural killer (NK) cells, which function more in a macrophage-like role in host defense against infection and malignancy. An understanding of normal lymphopoiesis requires knowledge of individual cell characteristics and expected responses of these cells to disease states.

LYMPHOID STEM CELLS

The earliest lymphoid stem cell is derived from the totipotent stem cell pool of the marrow. However, both B cells and T cells then mature in other lymphoid tissues. The thymus plays a major role in developing T cells. Precursors leave the marrow and migrate to the thymus, where they develop into immunocompetent cells. It is in the environment of the thymus that the T cell develops its critical ability to distinguish self from non-self and where errors in development form the basis for most, if not all, autoimmune disease. The stages of T-cell development in the thymus are well defined and form the basis for the clinical approach to the classification of T-cell malignancies.

B-cell development takes place in the marrow and peripheral lymphoid tissues, the lymph nodes, and spleen. The stages of B-cell development are not as clearly defined as those of T cells, forming more of a continuum leading to the end stage plasma cell. In addition to their classical role in the production of antibodies, B cells also serve as antigen-presenting cells. They have the ability to localize and process antigens from the environment and to present these antigens to other cells of the immune system just like macrophages. Regulatory T cells largely control their development and function. Therefore, it is sometimes difficult when presented with a disease secondary to immune dysfunction to assign root cause to the B- or T-cell system simply because the 2 systems are so intimately intertwined.

The Immune Network

One important concept for disorders of the immune system is the "immune network." Cells of the immune system make no basic distinction between internal antigen (ie, a component of self) and external antigen (ie, a pathogen or molecule arising from mutation or transplantation). All chemical structures in the body, including proteins, carbohydrates, and to a lesser extent lipids, are recognized by immune cells. This includes the components and products of the immune cells themselves. The "immune network" is balanced in such a way, however, that those cells that recognize self-antigens are suppressed but not eliminated, and those cells recognizing foreign antigens are stimulated but not allowed to become predominant. Thus, the immune system can be looked on as a balanced network of positive and negative interactions that is controlled by intertwined feedback ...

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