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Lymphocytes are a heterogeneous collection of cells that can be distinguished from other leukocytes by their characteristic morphology. 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. There are many lymphocyte subpopulations that can appear similar by morphology but have distinct antigen 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 microscopy of lymphocytes and plasma cells and the major surface antigens that are characteristic of each lymphocyte type.

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: CD, clusters of differentiation; Ig, immunoglobulin; MHC, major histocompatibility complex; NK, natural killer; TFH, follicular helper T-cells; Treg, T-regulatory cell.

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 mid 20th century, an 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, and that the marrow was the bursa equivalent in humans (human B cells therefore could represent marrow-derived cells, a happy coincidence). This discovery coupled with descriptions of inherited absence of the thymus leading to loss of cellular immunity but retention of humoral immunity and cases of retention of cellular immunity in children who were deficient in antibody production, eventually led to our current understanding of the division of labor among what originally appeared to be a common lymphocyte pool, morphologically. The later advent of monoclonal antibodies against numerous surface antigens coupled with flow cytometry, in vitro functional assays, molecular techniques to distinguish between B cells and T cells, and experiments using inbred strains of mice have brought us to our current state of knowledge of the immune response and its abnormalities.

Flow cytometry identifies a multitude of lymphocyte subsets based on antigen expression patterns. These immunophenotypic subsets correlate closely with function as determined by in vitro and in vivo testing. Three major blood lymphocyte functional subsets have been identified: T lymphocytes, B lymphocytes, and natural killer (NK) cells. The marrow and thymus contain precursor cells that resemble lymphocytes but lack function without differentiation and maturation into various lymphocyte subsets. Plasma cells are terminally differentiated B lymphocytes that produce immunoglobulin and mostly reside in marrow, lymph nodes, and other lymphoid tissues (see ...

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