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
