REVIEW doi: 10.1111/j.1365-3083.2006.01818.

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Antibody-Mediated Regulation of the Immune

Response
F. Hjelm, F. Carlsson, A. Getahun & B. Heyman

Department of Genetics and Pathology,
Uppsala University, Uppsala, Sweden
Received 10 May 2006; Accepted in revised
form 13 June 2006
Correspondence to: Dr B. Heyman, Department
of Genetics and Pathology, Rudbeck
Laboratory, Uppsala University, SE-751 85
Uppsala, Sweden. E-mail: birgitta.heyman@
genpat.uu.se
Abstract
Antibodies administered in vivo together with the antigen they are specific for
can regulate the immune response to that antigen. This phenomenon is called
antibody-mediated feedback regulation and has been known for over 100 years.
Both passively administered and actively produced antibodies exert immuno-
regulatory functions. Feedback regulation can be either positive or negative,
resulting in >1000-fold enhancement or >99% suppression of the specific
antibody response. Usually, the response to the entire antigen is up- or down-
regulated, regardless of which epitope the regulating antibody recognizes. IgG
of all isotypes can suppress responses to large particulate antigens like erythro-
cytes, a phenomenon used clinically in Rhesus prophylaxis. IgG suppression
works in mice lacking the known Fc-c receptors (FccR) and a likely mechan-
ism of action is epitope masking. IgG1, IgG2a and IgG2b administered
together with soluble protein antigens will enhance antibody and CD4+ T-cell
responses via activating FccR, probably via increased antigen presentation by
dendritic cells. IgG3 as well as IgM also enhance antibody responses but their
effects are dependent on their ability to activate complement. A possible
mechanism is increased B-cell activation caused by immune complexes
co-crosslinking the B-cell receptor with the complement-receptor 2/CD19
receptor complex, known to lower the threshold for B-cell activation. IgE-anti-
bodies enhance antibody and CD4+ T-cell responses to small soluble proteins.
This effect is entirely dependent on the low-affinity receptor for IgE, CD23,
the mechanism probably being increased antigen presentation by CD23+ B
cells.

can enhance antibody responses albeit by different mecha-

Introduction
It is remarkably difficult to generate an antibody response
to small soluble protein antigens without using adju-
vants, a fact referred to by Charlie Janeway as ‘the immu-
nologist’s dirty little secret’. Therefore, a significant part
of our knowledge about antibody responses stems from
studies of mice immunized with antigens in adjuvants.
In contrast, antibody feedback regulation is studied in
systems where antibodies and antigens are administered
in physiological salt solutions either as pre-formed com-
plexes or within hours of each other. In this situation,
antibodies can function as natural adjuvants, and potent
primary and secondary antibody responses as well as
T-cell responses are generated (reviewed in [1, 2]). Anti-
bodies produced early in humoral responses, IgM and
IgG3, as well as later on, IgG1, IgG2a, IgG2b and IgE,
nisms. In other situations, antibodies can exert negative
effects on antibody responses. An interesting finding is
the dual effects of IgG1, IgG2a and IgG2b administered
with soluble protein antigens. Their enhancing effects
seem to be mediated via activating Fc-c receptors (FccR)
but the enhancement is simultaneously negatively regula-
ted via the inhibitory FccRIIB. Another example is the
ability of IgG to inhibit responses to erythrocytes which
takes place in the absence of the known FccR, notewor-
thy also in the absence of FccRIIB. This effect is prob-
ably caused by antibodies masking the antigen and
preventing its recognition by B cells.
Antibody-mediated feedback regulation has been
known for over a century [3] and has been extensively
reviewed elsewhere [1, 2]. The purpose of the present
review is to give a comprehensive summary of the four

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Journal compilation  2006 Blackwell Publishing Ltd. Scandinavian Journal of Immunology 64, 177–184 177
178 Antibody-Mediated Regulation of the Immune Response
..................................................................................................................................................................
major feedback pathways operating when antibodies and
external antigens form immune complexes in vivo.
IgG-mediated suppression of antibody responses
The most frequently studied antibody feedback pathway
is IgG-mediated suppression of responses to erythrocytes
[4, 5], although IgG can also suppress responses to pro-
teins administered in adjuvants [6]. All murine IgG sub-
classes can suppress anti-erythrocyte responses [7, 8] but
the efficiency of suppression correlates with affinity of the
IgG antibodies [7, 9]. Both primary and secondary anti-
body responses are suppressed whereas T-cell priming
appears to occur normally [10]. Remarkably, IgG admin-
istered several days after erythrocytes can suppress an
ongoing antibody response [11, 12] implying that the
antigen needs to be recognized by cells of the immune
system not only during the initiation of an antibody
response but also during the following days.
Three different mechanisms for how IgG exerts its
suppressive capacity have been proposed:
(1) IgG may by masking of antigenic epitopes prevent
specific B cells from recognizing and binding to the anti-
gen.
(2) IgG/erythrocyte complexes may be captured by
FccR+ phagocytes and eliminated more rapidly than
erythrocytes alone. This would remove antigen from areas
where it can be recognized by the immune system.
(3) IgG/erythrocyte complexes may co-crosslink the
B-cell receptor (BCR) with the inhibitory FccRIIB, also
expressed on the B-cell surface. This would lead to negat-
ive regulation of the B cell, mediated by immunoreceptor
tyrosine-based inhibitory motifs in FccRIIB acting on
immunoreceptor tyrosine-based activation motifs (ITAM)
in the BCR [13]. Such co-crosslinking inhibits B-cell
activation in vitro [14, 15].
The first mechanism, epitope masking, would function
without the IgG(Fc)-portion whereas the two latter
mechanisms would require intact IgG(Fc)-portions. Stud-
ies testing whether F(ab¢)2 fragments were suppressive or
not have given conflicting results (for discussion, see [10,
16]). In an alternative approach, FccR-deficient mice were
used to assay for FccR dependence and it was shown that
IgG suppresses equally well in wild-type mice as in mice
lacking all known FccR, including FccRIIB [10, 12].
These observations together with previous findings that
complement activation is not required for the suppressive
ability of IgG [17], suggest that an Fc-independent
mechanism is operative. Although direct evidence is diffi-
cult to obtain, epitope masking by IgG seems to be a
likely explanation (Fig. 1). This is in agreement with the
fact that not only IgG, but also IgM [4, 7, 18] and IgE
[10, 19] can in certain situations suppress anti-erythro-
cyte responses. Should epitope masking be the mechan-
ism, a more appropriate term for IgG-mediated
Journal compilation  2006 Blackwell Publishing Ltd. Scandinavian Journal of Immunology 64, 177–184
F. Hjelm et al.
Figure 1 Suggested mechanism for IgG-mediated suppression of anti-
body responses. Specific IgG (or IgE and IgM) antibodies bind to eryth-
rocytes and prevent specific B cells from binding to the antigen. Lack of
B-cell receptor (BCR) stimulation leads to absence of an antibody
response, perceived as ‘suppression’. T helper-cell induction is not inhib-
ited by IgG, neither in mice nor in vitro, although the antibody
responses are suppressed.
suppression may be IgG-mediated prevention of an anti-
body response.
The ability of IgG antibodies to suppress responses to
erythrocytes has been used clinically since the 1960s
[20]. Rhesus-negative women, carrying Rhesus-positive
fetuses, can be sensitized against fetal erythrocytes
acquired via transplacental haemorrhage. This sometimes
causes haemolytic disease of the newborn as maternal IgG
antibodies specific for fetal Rhesus-positive erythrocytes
can pass the placenta and destroy fetal erythrocytes. To
prevent this, IgG anti-Rhesus D (RhD) is routinely
administered to Rhesus-negative women after delivery of
a Rhesus-positive baby. The passively administered IgG
antibodies prevent an active immune response against
RhD and this treatment has dramatically decreased the
incidence of haemolytic disease of the newborn [21]. It
seems reasonable to assume that IgG-mediated suppres-
sion of responses to sheep erythrocytes (SRBC) in mice
reflects the IgG-mediated suppression of responses to
RhD-positive erythrocytes in Rh-negative women. How-
ever, a few discrepancies are worth noting (discussed in
[22]). In the human system, doses of IgG anti-RhD
which are too low to mask all D epitopes still result in
efficient inhibition of the anti-RhD response [23]. More-
over, IgG specific for another blood group antigen, Kell,
was in one study shown to suppress the anti-D response
to D+K+ erythrocytes in D)K) humans [24]. One poss-
ible explanation for the discrepancies between IgG-medi-
ated suppression in the murine and human systems could
be that the considerably lower responses to allogeneic
erythrocytes in humans is easier to suppress than the vig-
orous responses to sheep erythrocytes in mice. Therefore,
also an incomplete epitope masking may be sufficient to
lower the immunogenicity of the RhD-positive erythro-
cytes. Alternatively, antibodies may target an erythrocyte
for destruction via mechanisms that are not dependent on
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F. Hjelm et al. Antibody-Mediated Regulation of the Immune Response 179
..................................................................................................................................................................

FccR or complement. There is to date no evidence to genic TCR. Specific T cells expanded rapidly and peaked
support that Rh prophylaxis requires FccRIIB in vivo, 3 days after immunization [38] (Fig. 2). The enhanced
although this, based on in vitro studies, is sometimes T-cell response was followed by an enhanced OVA-speci-
assumed to be the mechanism. Although IgG-mediated fic antibody response and both T- and B-cell responses
suppression of antibody responses to sheep erythrocytes were dependent on activating FccR [38]. This observation
in vitro is dependent on FccRIIB, suppression in vivo is compatible with the idea that complexes of IgG and
works equally well in the absence of this receptor [12]. antigen are captured by FccR+ APC and that they
Therefore, one has to be careful when interpreting the in enhance immune responses in vivo via increased antigen
vivo relevance of findings made in vitro. presentation to specific T helper cells (Fig. 3). The biolo-
Although IgG antibodies are used with great success gical role of IgG-mediated enhancement is most likely to
to suppress anti-RhD responses in humans and easily help in the induction of an efficient memory response, as
suppress >99% of a vigorous anti-SRBC response in antigen-specific IgG would often be present in the circu-
mice, the biological role of this feedback pathway is lation when the immune system encounters a booster
probably not to completely suppress antibody responses. dose of an immunogen.
More likely, the masking of certain epitopes by high FccRIIB is the only inhibitory FccR and is expressed
affinity IgG antibodies emerging relatively early in an on most cells of the immune system except NK and T
immune response may give the immune system the cells. It exerts its negative regulation on ITAM-bearing
opportunity of responding also to other epitopes and receptors such as the BCR, FccRI, FccRIII, FccRIV and
thereby ensure a broader range of antibody specificities. FceRI [39]. This gives FccRIIB a central role in immu-
noregulation and it has been shown to negatively regulate
a number of immune responses such as B-cell activation,
IgG1-, IgG2a- and IgG2b-mediated enhancement
BCR-mediated antigen presentation, antigen presentation
of antibody responses
by DC, maturation of DC and release of mediators
Although IgG1, IgG2a and IgG2b suppress responses to
particulate antigens, they are able to enhance responses
when administered together with soluble protein antigens
such as ovalbumin (OVA), bovine serum albumin and
keyhole limpet haemocyanine (KLH). This dual effect is
indeed dependent on the type of antigen and not on dif-
ferences in the IgG antibodies used: one and the same
monoclonal trinitrophenyl (TNP)-specific IgG suppressed
SRBC-specific responses when administered with SRBC-
TNP but enhanced KLH-specific responses when admin-
istered with KLH-TNP [25, 26]. These IgG isotypes
enhance primary as well as memory responses [27–29]
and immunization with IgG1 anti-nitrophenyl (NP)/NP-
KLH complexes increases somatic mutations in NP-speci-
fic germinal centre B cells [30].
IgG1-, IgG2a- and IgG2b-mediated enhancement is
dependent on the presence of activating FccR and these
must be expressed on bone marrow-derived cells [29, 31].
In vitro and ex vivo, antigens complexed to IgG are cap-
tured by FccR-expressing antigen-presenting cells (APCs)
and presented more efficiently to CD4+ T cells than anti-
gen alone [32–36]. To test whether such a mechanism
also explains IgG-mediated enhancement of antibody
Figure 2 Visualization of proliferating ovalbumin (OVA)-specific CD4+
responses, we have used a system where expansion of
T cells after immunization with antigen/antibody complexes. Mice were
antigen-specific CD4+ T cells can be studied directly adoptively transferred with CD4+ T cells from DO11.10 mice, expres-
in vivo [37]. CD4+ T cells from DO11.10 mice, trans- sing a transgenic T-cell receptor (TCR) specific for an OVA-peptide on
genic for a T-cell receptor (TCR) recognizing an OVA- MHC-II Ad. The day after transfer, mice were immunized i.v. with
peptide together with MHC-II Ad, were transferred to 20 lg OVA-trinitrophenyl (TNP) alone or together with 50 lg mono-
clonal IgG3 anti-TNP, IgG2a anti-TNP or IgE anti-TNP. Seventy-two
syngeneic wild-type BALB/c mice. After immunization
hours after immunization spleens were removed, sectioned and analysed
with IgG2a anti-TNP/OVA-TNP intravenously without by confocal microscopy. OVA-specific T cells (red) are stained with a
adjuvants, the expansion of OVA-specific T cells was fol- monoclonal antibody specific for the transgenic OVA-specific TCR and
lowed using a monoclonal antibody specific for the trans- B cells (blue) are stained with anti-B220.

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Journal compilation  2006 Blackwell Publishing Ltd. Scandinavian Journal of Immunology 64, 177–184
180 Antibody-Mediated Regulation of the Immune Response
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Figure 3 Suggested mechanism for IgG1-, IgG2a- and IgG2b-mediated
enhancement of antibody responses. IgG1, IgG2a and IgG2b complexed
to soluble protein antigens bind to activating Fc-c receptors (FccR)
expressed on antigen-presenting cells (presumably dendritic cells). Com-
plexed antigen is internalized more efficiently than non-complexed anti-
gens. Antigenic peptides are presented on MHC-II to specific CD4+ T
cells which expand and interact with antigen-specific B cells, resulting
in an enhanced antibody response.
(reviewed in [40]). FccRIIB-deficient mice have increased
susceptibility to many autoimmune diseases [41] and
have increased anaphylactic reactions [42].
The role of the receptor in regulation of in vivo anti-
body responses has been studied using FccRIIB-deficient
mice. As IgG-mediated enhancement is severely impaired
in mice lacking activating FccR, but which have normal
levels of FccRIIB [31], FccRIIB is not required for
induction of enhancement. However, this receptor has a
negative effect on responses to IgG-complexed soluble
antigens, demonstrated by an enhanced IgG-mediated
enhancement in FccRIIB-deficient mice [31, 38]. The
response in FccRIIB-deficient mice to IgG-complexed
antigen was sometimes more than 100-fold higher than
in wild-type mice [31, 38]. Notably, FccRIIB does not
completely turn off antibody production but ‘permits’
IgG to enhance antibody responses, as demonstrated by
the enhancement seen in wild-type mice. This illustrates
the intricate balance between inhibitory and activating
effects mediated by IgG and FccR. The outcome of regu-
latory effects of IgG antibodies is dependent on factors
such as the expression level of activating and inhibitory
FccR, which are often co-expressed on the same cell. It
also depends on the IgG subclass composition, as differ-
ent subclasses have different ratios of activating-to-inhibi-
tory receptor binding [43].
IgM- and IgG3-mediated enhancement of
antibody responses
It has been known since the 1970s that complement fac-
tor C3 is important for the capacity of animals to mount
normal antibody responses to suboptimal doses of antigen
Journal compilation  2006 Blackwell Publishing Ltd. Scandinavian Journal of Immunology 64, 177–184
F. Hjelm et al.
[44]. With the availability of gene-targeted mice, it
became clear that deficiencies in classical [45, 46] but not
alternative [47] pathway components resulted in impaired
antibody responses, suggesting that antibodies were
involved. Mice where complement receptor 1 and 2
(CR1/CR2) was blocked by monoclonal antibodies or
deleted by gene targeting have a similar phenotype with
regard to antibody responses as animals lacking classical
pathway components [48–51]. CR1/CR2 are derived by
alternative splicing of the same gene. In mice, they are
expressed on B cells and follicular dendritic cells (FDC)
implying that one or both of these cells are the effector
cells.
IgM is an efficient complement activator and when
IgM is passively administered together with large anti-
gens like erythrocytes [5, 52], malaria parasites [53]
and KLH [54] it enhances the antibody responses. IgM
upregulates both primary [5, 52–54] and memory
responses [55] and increases affinity maturation [56].
The enhancing effect is only seen with suboptimal
doses of antigen [5] and in order to enhance, IgM
must be administered within a few hours of the anti-
gen. The ability of specific IgM to enhance antibody
responses requires a functioning complement system.
IgM cannot enhance in mice lacking C3 owing to
treatment with cobra venom factor [52] or in mice
lacking CR1/CR2 [57]. Mutated or monomeric IgM
molecules which no longer activate complement also
loose their enhancing effects [52, 54].
We recently found that IgG3 also can enhance anti-
body responses [58]. IgG3 enhances in mice lacking all
activating FccR [58] and in mice selectively lacking
FccRI [59], which is suggested to be the IgG3-binding
FccR [60]. Unlike IgE [61] and IgG2a [38], IgG3 did
not induce proliferation of specific T cells in vivo [59]
(Fig. 2). Enhancement was severely impaired in mice
lacking CR1/CR2 and in animals depleted of C3 by
treatment with cobra venom factor [58].
Thus, both IgG3 and IgM depend on the complement
system for their enhancing capacity.
Both isotypes are relatively T independent and both
are produced early in an immune response. One single
IgM molecule can activate complement [62], provided it
can change conformation. IgG3 has the capacity to self-
associate into multivalent complexes, giving it a high
functional affinity and probably also increasing the likeli-
hood of C1q binding [63, 64]. These factors may explain
why IgM and IgG3 utilize the complement system in
feedback enhancement and, speculatively, also why IgM
can only enhance responses to large antigens (which are
required to enable the huge IgM molecule to bind with
its five arms and change conformation). IgE and IgG1 are
unable to activate complement, whereas IgG2a and
IgG2b require the rather unlikely event that two IgG
molecules bind close enough on the antigen to cooperate
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F. Hjelm et al.
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in C1q-binding. Therefore, it seems logical that these
isotypes use Fc-receptors for their feedback-enhancing
effects.
It is not understood why complement has such a dra-
matic impact on antibody responses, but several, not
mutually exclusive, mechanisms are possible:
(1) Antibody/antigen/complement complexes co-cross-
link the BCR and the CR2/CD19 complex, known to
lower the threshold for B-cell activation [65] (Fig. 4).
(2) Antibody/antigen/complement complexes are cap-
tured by FDC in the spleen and lymph nodes, increasing
the effective concentration of antigen [54, 66–68].
(3) Antibody/antigen/complement complexes are endo-
cytosed efficiently via CR1/CR2 on B cells and presented
to T helper cells which in turn help B cells to produce
antibodies. In vitro, B cells can take up antigen via CR1/
CR2 and present to T cells [69–72], but in vivo studies
in adoptive transfer/hapten-carrier systems do not support
a role for complement in T helper-cell activation [45,
73].
Regardless of which mechanism(s) that cause anti-
body/complement-mediated enhancement, it remains to
be explained how a primary antibody response can be
dependent on classical (antibody induced) complement
activation: in naive mice very low amounts of specific
IgM or IgG3 is available to form complexes with the
antigen. One possibility is that capture of antigen by
natural IgM and IgG3 suffices to start complement acti-
vation in primary antibody responses. Once activation of
specific B cells has taken place, these will secrete anti-
gen-specific IgM and IgG3, further enhancing the posit-
ive feedback loop. In line with this, mice lacking
secretory IgM had impaired antibody responses [74–76]
which could be reconstituted by transfusion of IgM from
naive mice [74].
Figure 4 Suggested mechanism for IgM- and IgG3-mediated enhance-
ment of antibody responses. IgM and IgG3 forming a complex with
specific antigen activates complement leading to attachment of comple-
ment factors to the immune complexes. The IgM or IgG3/antigen/com-
plement complexes co-crosslink the B-cell receptor (BCR) to the CR2/
CD19 co-receptor complex and lowers the threshold for B-cell activa-
tion, thereby leading to enhanced antibody responses.
 2006 The Authors
Journal compilation  2006 Blackwell Publishing Ltd. Scandinavian Journal of Immunology 64, 177–184
Antibody-Mediated Regulation of the Immune Response 181
IgE-mediated enhancement of antibody responses
In the 1990s, in vitro experiments showed that IgE-com-
plexed antigens, binding to the low-affinity receptor for
IgE (CD23) on the surface of B cells, could be internal-
ized and presented efficiently to T helper cells [77, 78].
These observations led to the hypothesis that a physiolo-
gical role of IgE may be to capture antigens and enhance
T helper-cell activation [79]. We tested this idea in an
in vivo system where mice were immunized with mono-
clonal IgE anti-TNP together with various protein anti-
gens coupled to TNP and found that IgE indeed
upregulated carrier-specific antibody responses [80]. IgE
enhances responses to small soluble protein antigens but
not to erythrocytes or large proteins such as KLH [80,
81]. All isotypes, including IgE, are upregulated and the
IgG response peaks as early as 6 days after priming [81,
82]. The enhancing effect of IgE is mediated by CD23,
evidenced by lack of enhancement in mice where CD23
is blocked by a monoclonal antibody [80, 81] or in
CD23-deficient mice [61, 83, 84]. Lack of involvement of
the high-affinity IgE-receptor (FceRI) was confirmed by
the normal IgE-mediated enhancement in FcRc-chain-
deficient mice, which do not express FceRI [31].
IgE-mediated enhancement works normally in IL-4-
deficient mice [85]. As IL-4 is required for expression of
the CD23b isoform [86], this observation suggests that
enhancement is mediated via the constitutively expressed
CD23a isoform. In mice, CD23a is expressed only on B
cells and FDC. Adoptive transfer experiments demonstra-
ted that FDC are not involved, leaving the B cells as the
likely effector cells [84]. Therefore, should the IgE-
enhanced antibody response in vivo be caused by enhanced
presentation of antigenic peptides to T helper cells, in
analogy with in vitro findings [77, 78], it would imply
that B cells can activate naive T cells. This is usually
considered to be performed by DC [87], and to investi-
gate whether IgE/antigen complexes do indeed activate
specific T cells in vivo, we used the DO11.10 experimen-
tal system described above. IgE anti-TNP administered
together with OVA-TNP induced a marked proliferation
of OVA-specific CD4+ T cells peaking 3 days after
immunization [61] (Fig. 2). Enhancement of T-cell
responses required the presence of CD23 which had to be
expressed on B cells. However, once such cells were pre-
sent (in chimaeric mice), also CD23) B cells produced
enhanced levels of specific antibody after immunization
with IgE/antigen [61]. These observations are compatible
with the antigen presentation hypothesis suggesting that
the enhanced antibody levels are a result of increased
T-cell help to specific B cells (Fig. 5). IgE-mediated
enhancement, as well as all other feedback regulatory
pathways, is specific for the antigen within the immune
complex. This means that although all CD23+ B cells
regardless of BCR specificity, take up and present
182 Antibody-Mediated Regulation of the Immune Response
..................................................................................................................................................................
Figure 5 Suggested mechanism for IgE-mediated enhancement of anti-
body responses. IgE/antigen complexes bind to CD23 on B cells and are
internalized more efficiently than non-complexed antigens. Antigenic
peptides are presented on MHC-II to specific CD4+ T cells which
expand and interact with antigen-specific B cells, giving them required
help for an enhanced antibody response.
IgE/antigen to specific T cells, only B cells which are
able to recognize the antigen via their BCR receive cog-
nate T-cell help leading to antibody production. This
resembles previous in vitro findings, demonstrating that
unspecific B cells, via CR2, take up and present immune
complexes containing complement factors, but that only
antigen-specific B cells are stimulated to antibody pro-
duction [72]. Thus, when IgE is present, CD23+ B cells
in vivo seem to function like DC (which also lack specific-
ity for the antigen they present) but induce specific T
cells which then provide help to B-cells.
It has been suggested that IgE-mediated enhancement
of antibody responses may create a vicious circle in atopic
patients who already have high levels of allergen-specific
IgE ready to form complexes with allergen [88]. The bio-
logical role of IgE-mediated enhancement of antibody
responses is not clear. However, the magnitude of T-cell
proliferation observed after immunization with IgE and
20 lg of OVA-TNP [61] is similar to what was seen
after immunization with 2 mg of uncomplexed OVA
together with LPS [89]. This suggests that capture of low
doses of antigen by IgE is an efficient way of priming
CD4+ T cells and this may be important in situations
where little antigen is available. Although serum IgE lev-
els are generally low, local concentrations may be high.
As CD23 binds IgE also in the absence of antigen, B
cells may be pre-loaded with IgE, ready to capture anti-
gen and induce efficient CD4+ T-cell responses.
Acknowledgments
Work in the authors’ laboratory was supported by Agnes
and Mac Rudberg’s Foundation; Ellen, Walter and Lenn-
art Hesselman’s Foundation; Emil and Ragna Börjesson’s
Journal compilation  2006 Blackwell Publishing Ltd. Scandinavian Journal of Immunology 64, 177–184
F. Hjelm et al.
Foundation; Hans von Kantzow’s Foundation; Ankar-
strand’s Foundation; King Gustaf V:s 80 Years Founda-
tion; Lilly and Ragnar Åkerhams’s Foundation; The
Swedish Research Council; Ollie and Elof Ericsson’s
Foundation; The ‘Network for Inflammation research’
funded by the Swedish Foundation for Strategic Research;
The Swedish Society for Medical Research; and Uppsala
University.
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