Carbohydrate Antigens
295
α
(1
6) dextran, which induces only an
ASC
response,
primary
immunization
with
α
(1
6) dextran elicits both an ASC
response as well as the GC reaction.
In
addition,
α
(1
6)
dextran
but
not
α
(1
3)
α
(1
6) dextran is able to elicit an
antigen-specifc IgA response in a strain
oF mice that lack Functional T-cells. This
strain was generated by knocking out the
genes encoding T-cell receptor
β
and
δ
,
resulting in a complete deletion oF T-cells
in these animals.
Molecular
and
cellular
mechanisms
underlying the above observations are
largely unknown. Polysaccharides oF dis-
tinct physicochemical properties, showing
characteristic patterns in their cellular
compartment localization have been, how-
ever, recognized For some years. In the
spleen, macrophages located in various cel-
lular compartments were shown to retain
polysaccharides selectively. Acidic polysac-
charides were predominantly localized in
red pulp macrophages; neutral polysaccha-
rides were detectable exclusively or very
intensely in macrophages oF the marginal
zone oF the white pulp. Memory B-cells
to T-dependent and T-independent anti-
gens were Found in the marginal zone.
±ollicular localization oF some polysaccha-
rides was shown to be complement de-
pendent. Lipopolysaccharides (LPS) may
interact with host cells in a number oF di-
verse ways, as B-cell polyclonal activators
or as T-independent antigen perForming
specifc stimulations. The Former is be-
lieved to be associated in their interactions
with macrophages. Lipoarabinomannan oF
mycobacterial pathogens exhibits a wide
spectrum oF immunoregulatory Functions,
such as inhibition oF interFeron-mediated
activation oF murine macrophages, the
scavenging oF potential cytotoxic oxygen-
Free radicals, inhibition oF protein kinase
C activity, and evocation oF a large array
oF cytokines associated with macrophages.
This mycobacterial lipoglycan mediates
the production oF macrophage-derived cy-
tokines, which, in turn, may evoke many oF
the clinical maniFestations oF tuberculosis
and leprosy.
The above two dextrans are neutral
polysaccharides but show diFFerences in
their cellular compartment localization.
Dextran B1355S [
α
(1
3)
α
(1
6) dextran]
was detectable in splenic marginal zones
oF the white pulp, but not in GCs. Dextran
N279 [
α
(1
6) dextran] persisted, how-
ever, in both splenic germinal centers
and marginal zone. ThereFore, their cor-
responding B-cell clones were incubated
in vivo
in diFFerent microenvironments
and were interacting with diFFerent types
oF cells, such as macrophages, Follicular
dendritic cells, and so on. Expression oF
lectin-like receptors by some oF these cells
has been recently documented. ±or ex-
ample, mannose binding lectin (MBL) is
expressed by some dendritic cells, which
can bind dextrans. Involvement oF distinct
lineages or subtypes oF B-cells is another
important Factor that may influence the
pathway oF B-cell activation in an immune
response. ±¨orster and Rajewsky demon-
strated that in BALB/c mice, the dominant
λ
1 response to B1355S
α
(1
3)
α
(1
6)
dextran is derived, at least in part, From
cells oF the B-1 lineage. A broad repertoire
oF anti-
α
(1
6) dextrans, associated with
multiple V
H
and V
L
genes and solely with
κ
L chains, suggests, perhaps, that diFFerent
lineages or subsets oF B-cells are involved
in anti-
α
(1
6) dextran responses.
5.3
Delayed Maturation of Anticarbohydrate
Responses
The delayed maturation oF antibody re-
sponse is a common characteristic oF TI
previous page 969 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 971 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off