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CHAPTER 73 DEFINITION AND HISTORY

THE STRUCTURE OF Lymphocytes and plasma cells first were described in 1774 and 1875,
respectively. Studies during the subsequent 75 years with improved his-
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LYMPHOCYTES AND tologic techniques and light microscope optics furthered understand-
ing of the lymphoid organs and the distribution of lymphocytes. By
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the mid-20th century, awareness that the immune system had at least
PLASMA CELLS 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
Natarajan Muthusamy and Michael A. Caligiuri* 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). This discovery coupled
SUMMARY with descriptions of inherited absence of the thymus leading to loss of
cellular immunity but retention of humoral immunity and cases of reten-
Lymphocytes are a heterogeneous population of blood cells that can be tion of cellular immunity in children who were deficient in antibody
distinguished from other leukocytes by their characteristic morphology and production, eventually led to our current understanding of the division
of labor among what originally appeared to be a common lymphocyte
structural features. Mature lymphocytes can be divided into several func- pool, morphologically. The later advent of monoclonal antibodies against
tional types and subtypes based on their organs of development and func- numerous surface antigens coupled with flow cytometry, in vitro func-
tion. The major classes of lymphocytes include T cells, B cells, and natural tional assays, molecular techniques to distinguish between B cells and
killer (NK) cells. T lymphocytes develop in the thymus (Chaps. 6, 74, and T cells, and experiments using inbred strains of mice brought us to our
76) and are exported to the blood and lymphoid organs. They are respon- current state of knowledge of the immune response and its abnormalities.
sible for cell-mediated cytotoxic reactions and for delayed hypersensitivity Flow cytometry identifies a multitude of lymphocyte subsets based
responses (Chap. 76). T lymphocytes also produce the cytokines that regulate on antigen expression patterns. These immunophenotypic subsets cor-
immune responses and provide helper activity for B cells. B lymphocytes can relate closely with function as determined by in vitro and in vivo testing.
capture, internalize, and present antigens to T cells and are the precursors T lymphocytes, B lymphocytes, and natural killer (NK) cells represent
of immunoglobulin-secreting plasma cells (Chap. 75). NK cells account three major blood lymphocyte functional subsets. The marrow and thy-
for innate immunity against infectious agents and transformed cells that mus contain precursor cells that resemble lymphocytes but lack func-
tion without differentiation and maturation into various lymphocyte
have altered expression of transplantation antigens (Chap. 77). Blood T and subsets. Plasma cells are terminally differentiated B lymphocytes that
B lymphocytes are indistinguishable by light and electron microscopy. NK produce immunoglobulin and mostly reside in marrow, lymph nodes,
cells tend to be larger cells with relatively large granules scattered in their and other lymphoid tissues. (Chap. 6).
cytoplasm. B cells can mature into plasma cells upon activation by engage-
ment with antigen or with certain B cell mitogens. Although the different MICROSCOPY AND HISTOCHEMISTRY
lymphocyte subpopulations appear similar by morphology they have distinct
surface and intracellular protein expression patterns. These subpopulations, OF NORMAL BLOOD LYMPHOCYTES
as defined by antigen expression, reflect different functional subsets, mat-
uration stages, and activation stages. This chapter describes the light and LIGHT MICROSCOPY
transmission electron microscopic structures of lymphocytes and plasma Classic studies of blood and tissues defined lymphocytes as spherical
cells and the major structural features reflected by surface antigens that are and/or ovoid cells that have diameters from 6 to 15 μm when flattened
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characteristic of each lymphocyte type. The chapter also provides informa- on glass slides. Some of these studies described two separate broad
tion on biophysical and biochemical features of human lymphocytes. types of lymphocytes based on size: small lymphocytes with diame-
ters of 6 to 9 μm and large lymphocytes with diameters of 9 to 15 μm.
Patients with acute viral illnesses have increased numbers of circulat-
ing large, “reactive,” lymphocytes. Other illnesses, such as infection
with Bordetella pertussis and autoimmune disorders, can cause blood to
have increased small lymphocytes or lymphocytes with plasma cell-like
morphology (Chap. 78). The mean absolute number of circulating small
Acronyms and Abbreviations: ADAM, a disintegrin and a metalloprotease; BTK, lymphocytes in normal adults is 2.5 × 10 /L (Chap. 2). Children have
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Bruton tyrosine kinase; CD, cluster of differentiation; Ig, immunoglobulin; lck, leuko-
cyte tyrosine kinase; LGL, large granular lymphocyte; MHC, major histocompatibility higher lymphocyte counts that trend downward until they reach adult
complex; NK, natural killer; TCR, T-cell receptor; TdT, terminal deoxynucleotidyl trans- levels at approximately 8 to 10 years of age (Chap. 7). 8
ferase; T , follicular helper T cells; Th, T helper cells; T , T-regulatory cell; ZAP-70, Most lymphocytes in normal blood are small with an ovoid or
REG
FH
zeta-associated protein of 70 kDa. kidney-shaped nucleus that stains purple, has densely packed nuclear
chromatin, and occupies approximately 90 percent of the cell area
(Fig. 73–1A and B) by Romanowsky polychromatic stains (e.g., Giemsa
or Wright) of air-dried films. A small rim of cytoplasm stains light blue.
Nucleoli rarely are observed in Wright-stained films, but nucleoli in
these cells may become visible in certain preparations, such as cytospin
* This chapter was written by H. Elizabeth Broome in the 8th edition and slides, or after prolonged storage in anti-coagulated blood collection
some of the text and images have been retained. tubes.

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