Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

B CELLS AND IMMUNOGLOBULINS
1317
intracellular
µ chain
µ chain
surrogate
L chain
µ chain
L chain
IgM
IgM
BCRs
IgD
B
B
δ chain
lymphoid
progenitor cell
pro-B cell
pre-B cell
immature
naive B cell
mature
naive B cell
DEVELOPMENT IN BONE MARROW
PERIPHERAL
LYMPHOID ORGANS
leave the bone marrow, they start to produce IgD BCRs as well, with the same
antigen-binding site as the IgM BCRs. These cells are now called mature naïve B
cells, as they can now respond to their specific foreign antigen in peripheral lymphoid
organs (Figure 24–24). IgM is also the major class of antibody secreted into
the blood in the early stages of a primary antibody response on first exposure to
an antigen. In its secreted form, IgM is a wheel-like pentamer composed of five
four-chain units, giving it a total of 10 antigen-binding sites that allow it to bind
strongly to pathogens; in its antigen-bound form, IgM is highly efficient at activating
complement, which is important in early antibody responses to pathogens.
The major antibody class in the blood MBoC6 is IgG. m25.22/24.25 These antibodies are four-chain
monomers (see Figure 24–23), and they are produced in especially large quantities
during secondary antibody responses. The tail region of some subclasses
of IgG antibodies that are bound to antigen can activate complement and also
bind to specific receptors on macrophages and neutrophils. Largely by means of
such Fc receptors (so-named because antibody tails are called Fc regions), these
phagocytic cells bind, ingest, and destroy infecting microorganisms that have
become coated with the IgG antibodies produced in response to the infection;
the activated Fc receptors also signal the phagocyte to secrete pro-inflammatory
cytokines (Movie 24.4).
The tail region of IgE antibodies binds to another class of Fc receptors on the
surface of mast cells in tissues and of basophils in the blood. Because antigen-free
IgE antibodies bind with high affinity to such Fc receptors, the antibodies act as
antigen receptors on these cells. Antigen binding to the bound antibodies activates
the Fc receptors and stimulates the cells to secrete a variety of cytokines
and biologically active amines, especially histamine, which causes blood vessels
to dilate and become leaky; this helps leukocytes, antibodies, and complement
components to enter sites where mast cells have been activated. The release of
amines from mast cells and basophils is largely responsible for the symptoms
of such allergic reactions as hay fever, asthma, and hives. In addition, mast cells
secrete factors that attract and activate leukocytes called eosinophils, which also
have Fc receptors that bind IgE molecules and can kill extracellular parasitic
worms, especially if the worms are coated with IgE antibodies (see Figure 24–6).
IgA is the principal antibody class in secretions, including saliva, tears, milk,
and respiratory and intestinal secretions. Yet another class of Fc receptors, located
on the relevant epithelial cells, guides the secretion by binding antigen-free IgA
dimers and transporting them across the epithelium. The properties of the various
classes of antibodies in humans are summarized in Table 24–2.
All classes of Ig can be made in a membrane-bound form, as well as in a soluble,
secreted form. The two forms differ only in the C‐terminus of their heavy
chain. The heavy chains of membrane-bound Ig molecules (BCRs) have a transmembrane
hydrophobic C‐terminus, which anchors them in the lipid bilayer of
the B cell’s plasma membrane. The heavy chains of secreted antibody molecules,
by contrast, have instead a hydrophilic C‐terminus, which allows them to escape
from the cell. The switch in the character of the Ig molecules made occurs because
the activation of B cells by antigen and helper T cells induces a change in the way
in which the heavy-chain RNA transcripts are made and processed in the nucleus
(see Figure 7–59).
Figure 24–24 Stages of B cell
development. All of the stages shown
occur before the cells bind their specific
antigen. The first cells in the B cell lineage
that make Ig are called pro‐B cells; they
make μ heavy chains, which remain in the
endoplasmic reticulum until a special type
of light chain is made called a surrogate
light chain. The surrogate light chains
substitute for genuine light chains and
assemble with μ chains to form a receptor
molecule that inserts into the plasma
membrane. The cells are now called pre‐B
cells. Signaling from this pre‐B cell receptor
allows the cells to make bona fide light
chains, which combine with μ chains to
form four-chain IgM molecules that serve
as cell-surface BCRs on immature naïve
B cells. After these cells leave the bone
marrow, they start to express IgD BCRs as
well, which have the same antigen-binding
sites as the IgM BCRs; it is this mature
naïve B cell that reacts with its specific
foreign antigen in peripheral lymphoid
organs.