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Lymphocytes are a heterogeneous population of blood cells that can be distinguished from other leukocytes by their characteristic morphology and structural features. Mature lymphocytes can be divided into several functional types and subtypes based on their organs of development and function. The major classes of lymphocytes include T cells, B cells, and natural killer (NK) cells. T lymphocytes develop in the thymus (Chaps. 5, 74 and 76) and are exported to the blood and lymphoid organs. They are responsible for cell-mediated cytotoxic reactions and for delayed hypersensitivity responses (Chaps. 74 and 76). They also produce the cytokines that regulate immune responses and provide helper activity for B cells. B lymphocytes can capture, internalize, and present antigens to T cells and are the precursors of immunoglobulin-secreting plasma cells (Chap. 75). NK cells account for innate immunity against infectious agents and transformed cells that have altered expression of transplantation antigens (Chap. 20). Blood T and B lymphocytes are indistinguishable by light and electron microscopy. Natural killer cells tend to be larger cells with relatively large granules scattered in their cytoplasm. B cells can mature into plasma cells upon activation by engagement with antigen or with certain B-cell mitogens. Although the different lymphocyte subpopulations appear similar by morphology, they have distinct surface and intracellular protein expression patterns. These subpopulations, as defined by antigen expression, reflect different functional subsets, maturation stages, and activation stages. This chapter describes the light and transmission electron microscopic structures of lymphocytes and plasma cells and the major structural features reflected by surface antigens that are characteristic of each lymphocyte type.

Acronyms and Abbreviations

ADAM, a disintegrin and a metalloprotease; ATP, adenosine 5'-triphosphate; BLINK, B-cell linker protein; Btk, Bruton tyrosine kinase; CCR, Chemokine receptor; CD, clusters of differentiation; HLA, human leukocyte antigen; Ig, immunoglobulin; IL-5Ra, Interleukin-5 receptor alpha; LAT, linker for activation of T cells; lck, leukocyte tyrosine kinase; LGL, large granular lymphocyte; MHC, major histocompatibility complex; NK, natural killer; STAT-3, Signal transducer and activator of transcription 3; TCR, T-cell receptor; TFH, follicular helper T cells; TH17 T-helper-17 cell; Treg, T-regulatory cell; ZAP-70, zeta-associated protein of 70 kDa.


Lymphocytes and plasma cells first were described in 1774 and 1875, respectively.1 Studies during the subsequent 75 years with improved histologic techniques and light microscope optics furthered understanding of the lymphoid organs and the distribution of lymphocytes.2–6 By the mid-20th century, awareness that the immune system had at least two components, one governing humoral immunity and one governing cellular immunity, led to early concepts of different lymphocyte subsets. Also, at the same time came the discovery that the thymus and bursa of Fabricius in birds were the source of what came to be known as T (thymic-derived) and B (bursa-derived) lymphocytes, respectively. In humans, the marrow is the bursa equivalent, and human B cells therefore ...

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