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
1319
variable region
of heavy chain
hypervariable
regions
hypervariable regions
of heavy chain
antigen-binding
site
Figure 24–26 Ig hypervariable regions.
Highly schematized drawing of how the
three hypervariable regions in each light
and heavy chain together form each
antigen-binding site of an Ig protein.
variable
region of
light chain
S S
S S
S S
S S
hypervariable
regions of
light chain
sheets held together by a disulfide bond; the variable domains are unique in that
each has its particular set of hypervariable regions, which are arranged in three
hypervariable loops that cluster together at the ends of the variable domains to
form the antigen-binding site (Figure 24–27B).
MBoC6 25.31/24.27
Ig Genes Are Assembled From Separate Gene Segments During
B Cell Development
Even in the absence of antigen stimulation, a human can probably make more
than 10 12 different Ig molecules—its preimmune, primary Ig repertoire. The primary
repertoire consists of IgM and IgD proteins and is apparently large enough
to ensure that there will be an antigen-binding site to fit almost any potential
V H
V H
hypervariable loops
S
S
C H 1 C H 1
S S
NH 2
S
S
S
S
S
V L
C L
V L
S
S
S
S S
S
S
S S
S S
S
S
S
S
C L
C H 2
S
S
S
S
C H 2
disulfide
bond
variable domain
of light chain (V L )
C H 3
S
S
S
S
C H 3
(A)
COOH
constant domain
of light chain (C L )
(B)
Figure 24–27 Ig domains. (A) The light and heavy chains in an Ig protein are each folded into similar repeating domains. The variable domains
(shaded in blue) of the light and heavy chains (V L and V H ) make up the antigen-binding sites, while the constant domains (shaded in gray) of the
heavy chains (mainly C H 2 and C H 3) determine the other biological properties of the protein. The heavy chains of IgM and IgE do not have a hinge
region and have an extra constant domain (C H 4). Hydrophobic interactions between domains on adjacent chains help hold the chains together in the
Ig molecule: V L binds to V H , C L binds to C H 1, and so on. (B) X-ray crystallography-based structures of the Ig domains of a light chain (Movie 24.5).
Both the variable and constant domains have a similar overall structure, consisting of two β sheets joined by a disulfide bond (red). Note that all the
hypervariable regions (black) form loops at the far end of the variable domain, where they come together to form part of the antigen-binding site. All
Igs are glycosylated on their C H 2 domains (not shown); the attached oligosaccharide chains vary from Ig to Ig and can greatly influence the biological
properties of the protein, largely by affecting its binding to Fc receptors on immune cells.