Page 524 - Review of Medical Microbiology and Immunology ( PDFDrive )

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mebooksfree.com mebooksfree.com mebooksfree.com B CELLS mebooksfree.com mebooksfree.com
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CHAPTER 58 Cellular Basis of the Immune Response
513
CD8 (cytotoxic) T cells. (These cells are also called suppres-
sor T cells.) TReg cells are 5% to 10% of the CD4-positive
B cells perform two important functions: (1) they differen-
cells and are characterized by possessing the CD25 marker.
tiate into plasma cells and produce antibodies, and (2) they
TReg cells produce FoxP3, a regulator of transcription
can present antigen to helper T cells.
of various genes. A hallmark of TReg cells that are
expressing FoxP3 is the synthesis of the inhibitory sur-
face protein, CTLA-4. (Recall that CTLA-4 inhibits
During embryogenesis, B-cell precursors are recognized first
costimulation by the B7:CD28 complex.) Individuals whose
in the fetal liver. From there they migrate to the bone mar-
TReg cells lack the ability to make FoxP3 are predisposed Origin
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row, which is their main location during adult life. Unlike T
mebooksfree.com mebooksfree.com mebooksfree.com have μ heavy chains in the cytoplasm. The maturation of B mebooksfree.com
to autoimmune diseases such as systemic lupus erythema-
cells, they do not require the thymus for maturation. Pre–B
tosus and a rare X-linked disease characterized by polyen-
cells lack surface immunoglobulins and light chains but do
docrinopathy and enteropathy (IPEX).
When there is an imbalance in numbers or activity
between CD4 and CD8 cells, cellular immune mechanisms
cells has two phases: the antigen-independent phase consists
of stem cells, pre–B cells, and B cells, whereas the antigen-
are greatly impaired. For example, in lepromatous leprosy
dependent phase consists of the cells that arise subsequent to
there is unrestrained multiplication of Mycobacterium
the interaction of antigen with the B cells (e.g., activated B
leprae, a lack of delayed hypersensitivity to M. leprae anti-
cells and plasma cells) (Figure 58–8).
gens, a lack of cellular immunity to that organism, and an
For pre–B cells to differentiate into B cells, a signal
excess of CD8 cells in lesions. Removal of some CD8 cells
can restore cellular immunity in such patients and limit
M. leprae multiplication. In acquired immunodeficiency
required. A mutation in the gene encoding this protein
syndrome (AIDS), the normal ratio of CD4: CD8 cells transduction protein called Bruton’s tyrosine kinase is
causes X-linked agammaglobulinemia in which immuno-
globulins (e.g., IgM, IgG) are not made and B cells are
(>1.5) is greatly reduced. Many CD4 cells are destroyed by
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mebooksfree.com mebooksfree.com mebooksfree.com for antigens. This surface IgM is a monomer, in contrast to mebooksfree.com
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absent. Severe infections caused by pyogenic bacteria occur
HIV, and the number of CD8 cells increases. This imbal-
in these patients.
ance (i.e., a loss of helper activity and an increase in sup-
B cells display surface IgM, which serves as a receptor
pressor activity) results in a susceptibility to opportunistic
infections and certain tumors.
One important part of the host response to infection is
circulating IgM, which is a pentamer. The monomeric IgM
on the surface has an extra transmembrane domain that
the increased expression of class I and class II MHC pro-
teins induced by various cytokines, especially interferons
anchors the protein in the cell membrane that is not present
such as gamma interferon. The increased amount of MHC
in the circulating pentameric form of IgM. Surface IgD on
some B cells may also be an antigen receptor. Pre–B cells
proteins leads to increased antigen presentation and a more
vigorous immune response. However, certain viruses can
the bloodstream.
suppress the increase in MHC protein expression, thereby
B cells constitute about 30% of the recirculating pool of
enhancing their survival. For example, hepatitis B virus,
adenovirus, and cytomegalovirus can prevent an increase are found in the bone marrow, whereas B cells circulate in
small lymphocytes, and their life span is short (i.e., days or
mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com e Plasma cell mebooksfree.com mebooksfree.com
9
weeks). Approximately 10 B cells are produced each day.
in class I MHC protein expression, thereby reducing the
Within lymph nodes, they are located in germinal centers;
cytotoxic T-cell response against cells infected by these
within the spleen, they are found in the white pulp. They
viruses.
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Stem cell
Pre-B cells
B cells

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FIGURE 58–8
Maturation of B cells. B cells arise from stem cells and differentiate into pre–B cells expressing μ heavy chains in the cyto-
plasm and then into B cells expressing monomer IgM on the surface. This occurs independent of antigen. Activation of B cells and differentia-
tion into plasma cells is dependent on antigen. Cells to the left of the vertical dotted line do not have IgM on their surface, whereas B cells, to
the right of the vertical line, do have IgM. μ, mu heavy chains in cytoplasm; Y, IgM. (Reproduced with permission from Stites DP, Terr A, eds. Basic & Clinical
Immunology. 7th ed. Originally published by Appleton & Lange. Copyright 1991 McGraw-Hill.)
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