Antigen Presenting Cells (APCs)
381
9
B lymphocytes
B lymphocytes (short: B cells) can also
serve as APCs, in particular, in the phase
after a T-cell response has been ini-
tiated. In contrast to macrophages, B
cells are known for their constitutive
expression of MHC class II molecules.
Furthermore,
only
B
cells
and
some
medullary
thymic
epithelial
cells,
but
not other APCs, express the nonclassi-
cal MHC class II allele HLA-DO which
is thought to regulate antigen process-
ing in a B cell–speci±c manner. Similar
to macrophages, B cells need an ac-
tivation signal to express costimulatory
molecules, thus, avoiding interaction with
self-reactive T cells.
It has been known for a while that B cells
are the key players in a humoral immune
response, as they are the only cells of the
immune system which can produce and
secrete antibodies recognizing antigenic
molecules. We will focus here on the
capacity of B cells to function as APCs.
Interestingly, it is still open as to how
important B cells are in priming naive
T cells in natural immune responses.
This relates to the fact that B cells are
uniquely adapted to bind and internalize
mainly soluble molecules through their
B-cell receptor (BCR), which is surface
immunoglobulin
(cf
Fig. 2).
However,
during
a
bacterial
or
viral
infection,
particulate antigen is abundant but soluble
antigen is rare. Therefore, it is not very
likely that the limited number of B cells
will detect soluble antigen that is only
present at very low concentrations and
that such an event is needed to prime
a helper T cell. It is by far more likely
that the main task of B cells is to present
peptide antigens in the context of MHC
class II molecules in order to receive
a signal from activated T cells leading
to
their
differentiation
into
antibody-
secreting plasma cells.
9.1
Antigen-induced B-Cell Activation
The activation of B cells in an antigen-
speci±c manner is initiated by the bind-
ing of antigen to the BCR. The BCR
serves two key roles in B-cell activa-
tion: (1) antigen-mediated clustering of
the BCR–antigen complexes initiates a
signaling cascade; (2) BCR mediates en-
docytosis
of
BCR–antigen
complexes
into MIIC compartments where MHC
class II molecules capture antigenic pep-
tides to be presented to CD4
+
helper
T cells.
Delivery of signals by the BCR starts
upon clustering of at least two BCR com-
plexes.
In vivo
, clustering is thought to
occur by multivalent antigen. In resting
B cells as well as in B cells that have
undergone isotype switching, membrane
molecules are associated with two other
molecules, termed Ig
α
and Ig
β
.Bo
tho
f
them are disulphide-linked heterodimers.
The cytoplasmic domains of Ig
α
and Ig
β
contain immunoreceptor tyrosine-based
activation motifs (ITAMs), which are ty-
rosine enriched. Cross-linking of IgM or
IgD molecules brings several ITAMs into
closer proximity, thereby triggering sub-
sequent signaling events. Initiation of
signaling is accomplished via src fam-
ily protein tyrosine kinases, such as Lyn,
Fyn, or Blk, which are associated with
the BCR and trans-phosphorylate ITAMs.
Downstream signaling events ultimately
activate transcription factors such as Fos,
JunB, or NF-
κ
B that induce the expres-
sion of genes whose products facilitate
B-cell activation.
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