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Chapter 73: The Structure of Lymphocytes and Plasma Cells 1143

LYMPHOCYTE SURFACE ANTIGENS LYMPHOCYTE MEMBRANE
Lymphocyte subsets generally cannot be distinguished from one another The lymphocyte plasma membrane is composed of equal parts of weight
by morphology. Most resting lymphocytes appear as small round cells of protein and glycosphingolipids and 6 percent by weight of carbohy-
with a dense nucleus and little cytoplasm. However, this homogeneous drate. The molar ratio of cholesterol to phospholipid is approximately
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appearance is deceptive, as these cells comprise many functionally dis- 0.5. 64,65 Phosphatidylcholine is the predominant phospholipid in the
tinct subpopulations. lymphocyte plasma membrane, but phosphatidylethanolamine, phos-
These subsets can be distinguished through the differential expres- phatidylinositol, phosphatidylserine, and sphingomyelin are also pres-
sion of cell-surface proteins, each of which can be recognized by a spe- ent. Approximately half the membrane fatty acids are saturated. The
cific monoclonal antibody. Coupled with the biochemical analyses of membrane proteins are usually glycosylated.
the surface molecules that are recognized by each of these antibodies, The glycosphingolipids and protein receptors of lymphocytes
many lymphocyte surface antigens have been defined. often are organized in glycolipoprotein microdomains termed lipid
Typically, it is necessary to monitor for coexpression of two or rafts. 66,67 Such lipid rafts sequester various protein receptors, corecep-
more cell-surface proteins to define a functional subset of lympho- tors, and accessory molecules that together are involved in lymphocyte
cytes. The same cell-surface protein is often expressed by more than cell signaling, cytoskeletal reorganization, and/or membrane traffick-
one cell subset. For example, both helper and cytotoxic T cells express ing. As such, the surface molecules on lymphocytes are not randomly
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CD3, the proteins associated with the TCR for antigen (Chap. 76). distributed.
Expression of both CD3 and CD4 helps to distinguish mature Th cells
from cytotoxic T cells that express CD3 and CD8, and from other cells, Extracellular Membrane-Associated Enzymes (Ectoenzymes)
such as dendritic cells, that express CD4 but lack expression of CD3 Exposed on the exterior surface of lymphocytes are several enzymes
(Chap. 76). As noted above (see “CD4 and CD8 Lymphocyte Sub- called ectoenzymes (Table 73–2). Generally, the number of surface
sets”), T REG cells are defined by the coexpression of CD3, CD4, CD25, enzyme molecules is low compared with that of other surface molecules,
and cytoplasmic FoxP3. For these and other types of lymphocytes, it such as those involved in lymphocyte adhesion. This probably reflects
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is the expression of a characteristic constellation of surface and cyto- the fact that these molecules are catalytic and have a higher functional
plasmic molecules, rather than the expression of any one particular specific activity than do molecules involved in adhesion events, where
marker, that generally helps to distinguish one subset of lymphocytes multiple interactions over large surface areas are required. As such, it is
from another. possible that many more enzymes are present than the ones currently
Fluorescent probes also can be used to identify antigen-specific recognized because they are expressed at levels that are not detect-
lymphocytes. Each clone of B lymphocytes expresses Ig capable of able by conventional methods using monoclonal antibodies and flow
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binding a particular antigen (Chap. 75). The frequencies of B cells cytometry.
specific for one antigen are estimated to range from 1 in 100,000 to Some of the surface enzymes are involved in nucleotide metab-
1 in 1,000,000 cells or less. Populations of lymphocytes enriched for olism (see Table 73–2). For example, CD73 is an ecto-5′-nucleotidase
B cells binding to a specific antigen can be stained using anti- that catalyzes the 5′ dephosphorylation of purine and pyrimidine ribo-
gen coupled to probes, allowing for the detection and isolation of and deoxyribonucleoside monophosphates to nucleosides that can be
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antigen-specific B cells using flow cytometry. Alternatively, flow- taken up by transport systems. This ecto-5′-nucleotidase is attached
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based techniques can be used to monitor for antigen-specific B cells to the plasma membrane by a glycerol phosphatidylinositol anchor.
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that are activated by contact with antigen. T lymphocytes, how- In addition, lymphocytes express CD26, which is a membrane pro-
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ever, generally recognize antigen in the form of peptides nestled into tein that can associate with adenosine deaminase, the levels of which
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molecules of the MHC (Chap. 76). Thus identification and isolation of are increased after activation. The shedding of adenosine deaminase
antigen-specific T cells require more complex probes using multim- by stimulated cells may explain why plasma levels of this enzyme are
eric complexes comprised of specific peptide antigen complexed with increased in early HIV infection and in other diseases associated with
the relevant MHC molecule. 57 immune activation. 72
The ectoenzymes of nucleotide metabolism may regulate lym-
phocyte and granulocyte function at sites of inflammation. Activated
COMPOSITION OF LYMPHOCYTES T lymphocytes can release ATP, which, in turn, can bind to specific
plasma membrane ATP receptors. In addition, CD38 can catalyze the
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Unfortunately, few studies of the composition and biochemistry of
lymphocytes have used purified lymphocyte subpopulations. Because transient formation of cyclic adenosine 5′-diphosphate-ribose, a new
mature helper T cells are the predominant blood lymphocyte of normal second-messenger molecule directly involved in the control of calcium
adults, many reported biochemical parameters are most relevant to this homeostasis by means of receptor-mediated release of calcium from
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subpopulation. ryanodine-sensitive intracellular stores. The consequent increase in
calcium mobilization and phospholipid breakdown can provoke acti-
vation or death, depending on the target cell. Subsequently, the dephos-
ION AND WATER CONTENT phorylation of ATP generates adenosine, which can interact with A2
3
The resting blood lymphocyte has a mean cell volume of 200 μm and receptors on the plasma membranes of neutrophils, monocytes, and
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75
contains 71 ± 1.2 percent by weight of water. The total lymphocyte cat- lymphocytes. The engagement of A2 receptors elevates adenosine
ion content is 35 femtomoles (fmol) per cell, of which 22 to 28 fmol per 3′,5′-cyclic phosphate levels, counteracting the effects of ATP on cell
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cell is potassium, and 7.9 ± 3.2 fmol per cell is sodium. Lymphocyte activation. The deamination of adenosine permits the cycle to begin
membranes have both voltage-gated and calcium-activated potassium anew.
channels that regulate cell volume. Pharmacologic inhibition of these The ectodomains of several other surface antigens can possess prote-
channels blocks T-cell activation. The calcium content of resting lym- olytic activity. For example, CD10 (or CALLA) also has neutral endopep-
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phocytes has been estimated at 580 to 800 pmol/10 cells. Cytosolic tidase activity, and CD26 has dipeptidyl peptidase IV activity. These
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6
76
free calcium concentrations are relatively low in resting lymphocytes enzymes may play a role in modulating the binding of lymphocytes to
(approximately 0.1 μM) but increase severalfold after activation. 62 other cells and to the extracellular matrix. In addition, inhibition of the

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