382
Antigen Presenting Cells (APCs)
B-cell activation requires, in addition
to antigen, second signals, which may
be provided by complement proteins; for
example, C3d binds to the type 2 com-
plement–receptor CR2 on B cells (Fig. 8).
Since C3d binds covalently to microbial
antigens in the course of complement acti-
vation, antigen-C3d complexes can bridge
the BCR and CR2. Binding of C3d to
the B-cell complement receptor recruits
CD19 and the tetraspanin CD81 into
the complex. CR2-CD19-CD81 is often
called
the
B
cell
coreceptor complex.
Phosphorylation of the cytoplasmic tail
of CD19 by the BCR-associated kinases
leads to augmentation of the humoral
immune response by 100- to 1000-fold.
In summary, a proteolytic fragment of
complement, which is induced by mi-
crobes, provides the second signal for
B-cell activation. This is reminiscent of
T-cell activation depending not only on sig-
nal 1 (TCR-MHC-peptide interaction) but
also on costimulation (CD80/CD86-CD28
interaction).
9.2
Antigen Presentation Outside the Follicular
Center
Within 1 to 2 days after antigen admin-
istration, B cells recognize antigen in the
follicles of peripheral lymphoid organs,
are activated, and begin to migrate out
of the follicles toward the T-cell zones.
The initial encounters between antigen-
stimulated B and T cells occur at the
interphase of the follicles and the T-cell
zones (Fig. 9). In striking contrast to other
APCs, B cells do not migrate into tis-
sues where pathogens enter the body, but
thean
t
igenshavetobet
ranspo
r
tedin
to
lymph nodes or to the spleen via the lym-
phatic vessels or blood stream to meet
B cells.
9.2.1
B-cell Epitope versus T-cell Epitope
The three-dimensional molecular struc-
ture of an antigen that is recognized by
the BCR of a B cell is termed the
B-cell
epitope
, which is a conformational epitope.
MHC II
MHC I
CD40
CD81
CD19
CR2
Antigen
BCR
C3d
Signal 1:
Polyvalent antigen
binds to BCR
Signal 2:
C3d-antigen complex
bridges BCR and
CR2 – CD19 – CD81
MHC I
MHC II
CD40
CD80
CD86
BCR
Resting B cell
Activated B cell
Bcl-x
IL-4R
IL-2R
Fig. 8
Activation of B cells: resting B cells bind
polyvalent antigen via the B-cell receptor (BCR)
thereby generating signal1. The complement
factor C3d bridges the antigen with another
signaling complex consisting of the complement
receptor CR2, CD19, and CD81, thereby
generating signal 2. Activated B cells express
costimulatory molecules, for example, CD80 and
CD86, the IL-2 receptor (IL-2R), and the IL-4
receptor (IL-4R).
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