published: 11 January 2012
Regulation of B cell functions by the sialic acid-binding
receptors Siglec-G and CD22
Julia Jellusova†and Lars Nitschke*
Chair of Genetics, University of Erlangen, Erlangen, Germany
Anthony L. DeFranco, University of
California San Francisco, USA
Pablo Engel, University of Barcelona,
I-Hsin Su, NanyangTechnological
Lars Nitschke, Chair of Genetics,
University of Erlangen, Staudtstr. 5,
91058 Erlangen, Germany.
Julia Jellusova, Sanford-Burnham
Medical Research Institute, La Jolla,
To achieve an appropriate response, the BCR signal is interpreted in the context of other
stimuli and several additional receptors on the B cell surface participate in the modulation
of the signal. Two members of the Siglec (sialic acid-binding immunoglobulin-like lectin)
family, CD22 and Siglec-G have been shown to inhibit the BCR signal. Recent findings indi-
cate that the ability of these two receptors to bind sialic acids might be important to induce
tolerance to self-antigens. Sialylated glycans are usually absent on microbes but abundant
in higher vertebrates and might therefore provide an important tolerogenic signal. Since
the expression of the specific ligands for Siglec-G and CD22 is tightly regulated and since
Siglecs are not only able to bind their ligands in trans but also on the same cell surface this
might provide additional mechanisms to control the BCR signal. Although both Siglec-G
and CD22 are expressed on B cells and are able to inhibit BCR mediated signaling, they
also show unique biological functions. While CD22 is the dominant regulator of calcium
signaling on conventional B2 cells and also seems to play a role on marginal zone B cells,
Siglec-G exerts its function mainly on B1 cells and influences their lifespan and antibody
production. Both Siglec-G and CD22 have also recently been linked to toll-like receptor sig-
naling and may provide a link in the regulation of the adaptive and innate immune response
of B cells.
Keywords: Siglecs, B lymphocytes, BCR signaling, inhibitory signaling,TLR, autoimmunity, B1 cells
INTRODUCTION TO THE SIGLEC FAMILY
B cells are an important part of the immune system and through
production of antibodies crucially contribute to the humoral
immune response. Recognition of antigen by the B cell antigen
receptor (BCR) is the main event in the B cell immune response
the Siglec (sialic acid-binding immunoglobulin-like lectins) fam-
ily and have been shown to negatively regulate B cell signaling.
discusses their possible biological functions.
Siglecs are a family of sialic acid-binding proteins expressed on
cells of the immune system (Crocker et al., 2007) with the excep-
tion of myelin associated glycoprotein (MAG) which is expressed
on myelinating glia cells, suggesting a role in the nervous system
on other tissues in addition to cells of the immune system. The
expression of Siglec-6 has been observed on B cells and placental
trophoblasts (Patel et al., 1999; Brinkman-Van der Linden et al.,
2007) and Siglec-11 can be detected on macrophages and brain
microglia (Angata et al., 2002). However, the majority of Siglecs
seems to play a role mainly in the immune system in both human
(Table1). CD22 and Sialoadhesin have been found only on B cells
or macrophages (Crocker et al., 1994, 2007), respectively. Other
Siglecs are expressed more broadly. For example, Siglec-9 can be
B cells,however it might be also expressed on other cell types such
has been detected on B cells, NK cells, monocytes, dendritic cells,
and eosinophils (Munday et al., 2001).
Members of the Siglec family are expressed in different ver-
tebrates and are present in all investigated mammalian species
(Angata,2006). However,only four members of the Siglec family-
Sialoadhesin (Siglec-1), CD22 (Siglec-2), MAG, and Siglec-15 are
highly conserved throughout mammalian evolution. In contrast,
the group of CD33 related Siglecs is rapidly evolving and often
no clear orthologs can be assigned between different mammalian
species (Angata et al.,2004). Humans express a larger set of CD33
related Siglecs (CD33/Siglec-3, Siglec-4, -5, -6, -7, -8, -9, -10, -
11, -14, -16) than mice (CD33/Siglec-3, Siglec-E, -F, -G, -H) and
the distribution on different cell types seems to be unique for
each species as well. Interestingly Siglec-G is one of the few CD33
related Siglecs with a clear human ortholog – Siglec-10. In addi-
tion to sequence homology, both Siglec-G and Siglec-10 can be
detected on B cells suggesting that they might also share some
functional similarity (Munday et al., 2001).
All Siglecs share some structural features. They are transmem-
brane proteins with a variable number of immunoglobulin-like
domains in their extracellular portions and a cytoplasmic part
at the carboxy terminus. Located within the cytoplasmic tail are
January 2012 | Volume 2 | Article 96 | 1
Jellusova and NitschkeInhibitory Siglecs on B cells
Table 1 | Expression pattern of murine and human Siglecs on the cells of the immune system.
B cells T cellsNK cells Monocytes Macrophages Dendritic cellsNeutrophilsEosinophilsBasophils
The table summarizes the expression of murine and human Siglecs on different cell types of the immune system. Differences in expression levels or the frequency
of Siglec expressing cells in a given population are not depicted. CD22 is also known as Siglec-2, CD33 as Siglec-3, Sialoadhesin as Siglec-1. Sub, subpopulations (Li
et al., 2001; Zhang et al., 2004; Varki and Angata, 2006; Angata et al., 2007; Cao and Crocker, 2010).
sites for possible tyrosine phosphorylation. These tyrosines are
often part of the consensus sequence of immunoreceptor tyrosine
able to recruit Src homology 2 (SH2) domain containing signal-
ing molecules such as the tyrosine phosphatases SHP-1 or SHP-2.
Interaction with SHP-1 could be demonstrated for CD22 (Doody
et al., 1995), Siglec-7, Siglec-9 (Ikehara et al., 2004), and Siglec-10
well-characterized inhibitory receptors such as CD72, PIR-B, or
FcγRIIB (Nitschke et al., 1997) and therefore ITIM containing
Siglecs are expected to play an inhibitory role in cell signaling.
Indeed, several Siglecs have been reported to inhibit different
signaling pathways. Siglec-7 and -9 can inhibit TCR mediated sig-
naling (Ikehara et al., 2004), Siglec-G and CD22 are inhibitors
of the BCR signal (Nitschke et al., 1997; Hoffmann et al., 2007),
Siglec-E probably plays an inhibitory role in Toll-like receptor
(TLR)-mediated IFNβ production (Boyd et al., 2009). However,
some Siglecs lack ITIM motifs, associate with activating recep-
tors and are therefore thought to be activatory transmembrane
proteins (Crocker et al., 2007).
Unlike most other proteins from the immunoglobulin super-
family, Siglecs do not bind protein determinants but recognize
ification of glycoproteins in vertebrates and higher invertebrates,
but relatively rare outside the Deuterostomia lineage (Angata and
ous proteins creating a broad array of possible Siglec ligands. The
affinity can be influenced by the type of the sialic acid,the type of
linkage to the underlying oligosaccharide chain and also the pres-
ence of other proximal sugars (Angata, 2006). Some Siglecs show
strict ligand requirements and some recognize a broader range
of sialic acids. Given the complex expression pattern of Siglecs
on different cells of the immune system, the plasticity of possible
not surprising that Siglecs are believed to participate in many dif-
have been suggested to play a role in cell–cell adhesion (Schadee-
Eestermans et al., 2000), regulation of responses to tissue damage
(Chen et al., 2009), controlling allergic reactions of eosinophils
(Zhang et al., 2007), and maintenance of tolerance (Duong et al.,
2010).Yet, because of the complexity of Siglec biology and due to
recent discoveries of new Siglecs the exact biological function of
many Siglecs remains incompletely understood.
INHIBITION OF BCR SIGNALING BY Siglec-G AND CD22
Siglec-G and CD22 are the only two Siglecs reported to be
expressed on murine B cells so far. While CD22 appears to be
expressed exclusively on B cells, Siglec-G is expressed predomi-
on other cell types as well (Ding et al., 2007). Both Siglecs seem
to be able to associate with the BCR (Peaker and Neuberger,1993;
atively regulate BCR mediated signaling. Siglec-G has been shown
to be an important inhibitor on B1a cells,since Siglec-G-deficient
B1a cells show increased calcium signaling after anti-IgM stim-
ulation (Hoffmann et al., 2007). Siglec-G is also able to dampen
the BCR signal when transfected into DT40 cells, a B cell line
lacking endogenous Siglecs and widely used to study compo-
nents of the BCR signaling cascade. However, conventional B2
cells show normal calcium signaling in Siglec-G-deficient mice,
indicating a redundant function of Siglec-G in this B cell popu-
lation (Hoffmann et al., 2007). The dominant inhibitor in con-
ventional (B2) cells seems to be CD22 and CD22-deficient mice
show increased calcium signaling in these cells. While the exact
biochemical mechanism for the inhibition mediated by Siglec-G
pathways downstream of CD22.
CD22 contains six tyrosines in its cytoplasmic tail, three of
which are found within conventional ITIMs (Y783, Y843, Y863),
one is part of an ITIM-like motif (Y817), and one is needed for
the recruitment of Grb2 (Y828; Otipoby et al., 2001). CD22 is
rapidly phosphorylated after BCR crosslinking and docking sites
for different signaling molecules are created. The Src kinase Lyn
plays a central role in this process (Smith et al.,1998). B cells from
stimulation and as a consequence SHP-1 recruitment to CD22 is
ing from other receptors and believed to be the central signaling
molecule mediating CD22 inhibition. CD22 is unable to inhibit
Frontiers in Immunology | B Cell Biology
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Jellusova and NitschkeInhibitory Siglecs on B cells
of systemic lupus erythematosus.
Genes Immun. 7, 592–599.
Hennet, T., Chui, D., Paulson, J. C., and
Marth, J. D. (1998). Immune reg-
ulation by the ST6Gal sialyltrans-
ferase. Proc. Natl. Acad. Sci. U.S.A.
Hoffmann, A., Kerr, S., Jellusova, J.,
Zhang, J., Weisel, F., Wellmann, U.,
R.,and Nitschke,L. (2007). Siglec-G
is a B1 cell-inhibitory receptor that
controls expansion and calcium sig-
Immunol. 8, 695–704.
Silver, K., Peng, K., Takatsu, K., and
Goodnow, C. C. (2007). Enhance-
ment and suppression of signal-
ing by the conserved tail of IgG
memory-type B cell antigen recep-
tors. J. Exp. Med. 204, 759–769.
Ikehara, Y., Ikehara, S. K., and Paulson,
J. C. (2004). Negative regulation of
T cell receptor signaling by Siglec-
7 (p70/AIRM) and Siglec-9. J. Biol.
Chem. 279, 43117–43125.
Jang, I. K., Cronshaw, D. G., Xie,
L. K., Fang, G., Zhang, J., Oh,
H., Fu, Y. X., Gu, H., and Zou,
Y. (2011). Growth-factor receptor-
bound protein-2 (Grb2) signaling
in B cells controls lymphoid folli-
Jellusova, J., Duber, S., Guckel, E.,
Binder, C. J., Weiss, S., Voll, R., and
Nitschke, L. (2010a). Siglec-G regu-
lates B1 cell survival and selection. J.
Immunol. 185, 3277–3284.
Jellusova, J., Wellmann, U., Amann,
K., Winkler, T. H., and Nitschke,
double-deficient mice have mas-
sively increased B1 cell numbers and
develop systemic autoimmunity. J.
Immunol. 184, 3618–3627.
Jin, L., Mclean, P. A., Neel, B. G.,
and Wortis, H. H. (2002). Sialic
acid binding domains of CD22 are
required for negative regulation of B
cell receptor signaling. J. Exp. Med.
John, B., Herrin, B. R., Raman, C.,
Wang, Y. N., Bobbitt, K. R., Brody,
B. A., and Justement, L. B. (2003).
The B cell coreceptor CD22 asso-
ciates with AP50, a clathrin-coated
pit adapter protein, via tyrosine-
dependent interaction. J. Immunol.
Kaneko, Y., Nimmerjahn,
from Fc sialylation. Science 313,
Kawasaki, N., Rademacher, C., and
Paulson, J. C. (2011). CD22 regu-
lates adaptive and innate immune
Kelm, S., Gerlach, J., Brossmer, R.,
Danzer, C. P., and Nitschke, L.
(2002). The ligand-binding domain
of CD22 is needed for inhibition of
the B cell receptor signal, as demon-
strated by a novel human CD22-
specific inhibitor compound. J. Exp.
Med. 195, 1207–1213.
Kono, M., Ohyama, Y., Lee, Y. C.,
of in vitro substrate specificities
Glycobiology 7, 469–479.
Lajaunias, F., Ibnou-Zekri, N., Fossati
Jimack, L., Chicheportiche,Y., Park-
Brighouse, G., and Izui, S. (1999).
Polymorphisms in the Cd22 gene of
ics 49, 991–995.
Lajaunias, F., Nitschke, L., Moll, T.,
Chicheportiche, Y., Parkhouse, R.
regulated expression and function
of CD22 in activated B-1 and B-2
Lanoue, A., Batista, F. D., Stewart, M.,
and Neuberger, M. S. (2002). Inter-
sialoglycoconjugates: innate recog-
nition of self to dampen B cell
autoreactivity? Eur. J. Immunol. 32,
Lau, C. M., Broughton, C., Tabor, A.
S., Akira, S., Flavell, R. A., Mamula,
M. J., Christensen, S. R., Shlomchik,
M. J., Viglianti, G. A., Rifkin, I. R.,
and Marshak-Rothstein, A. (2005).
RNA-associated autoantigens acti-
vate B cells by combined B cell
antigen receptor/Toll-like receptor
7 engagement. J. Exp. Med. 202,
Law, C. L., Sidorenko, S. P., Chan-
dran, K. A., Zhao, Z., Shen, S. H.,
Fischer, E. H., and Clark, E. A.
tyrosine phosphatase 1C, Syk, and
phospholipase C-gamma(1) upon B
cell activation. J. Exp. Med. 183,
Li, N., Zhang, W., Wan, T., Zhang, J.,
Chen, T., Yu, Y., Wang, J., and Cao,
tion of Siglec-10, a novel sialic acid
ily, from human dendritic cells. J.
Biol. Chem. 276, 28106–28112.
Martin, F., and Kearney, J. F. (2002).
Marginal-zone B cells. Nat. Rev.
Immunol. 2, 323–335.
Mary, C., Laporte, C., Parzy, D., San-
tiago, M. L., Stefani, F., Lajau-
nias, F., Parkhouse, R. M., O’Keefe,
T. L., Neuberger, M. S., Izui, S.,
and Reininger, L. (2000). Dys-
regulated expression of the Cd22
gene as a result of a short inter-
spersed nucleotide element inser-
tion in Cd22a lupus-prone mice. J.
Immunol. 165, 2987–2996.
Montecino-Rodriguez, E., Leathers, H.,
and Dorshkind, K. (2006). Identifi-
cation of a B-1 B cell-specified prog-
enitor. Nat. Immunol. 7, 293–301.
Munday, J., Kerr, S., Ni, J., Cornish, A.
L., Zhang, J. Q., Nicoll, G., Floyd,
H., Mattei, M. G., Moore, P., Liu, D.,
and Crocker, P. R. (2001). Identifi-
cation, characterization and leuco-
cyte expression of Siglec-10, a novel
human sialic acid-binding receptor.
Biochem. J. 355, 489–497.
Naito, Y., Takematsu, H., Koyama, S.,
Miyake, S., Yamamoto, H., Fuji-
nawa, R., Sugai, M., Okuno, Y., Tsu-
jimoto, G., Yamaji, T., Hashimoto,
Y., Itohara, S., Kawasaki, T., Suzuki,
A., and Kozutsumi, Y. (2007). Ger-
minal center marker GL7 probes
activation-dependent repression of
N-glycolylneuraminic acid, a sialic
acid species involved in the nega-
tive modulation of B-cell activation.
Mol. Cell. Biol. 27, 3008–3022.
Naka, T., Fujimoto, M., Tsutsui, H., and
Yoshimura, A. (2005). Negative reg-
ulation of cytokine and TLR sig-
nalings by SOCS and others. Adv.
Immunol. 87, 61–122.
Nakamura, K., Yamaji, T., Crocker, P.
R., Suzuki, A., and Hashimoto, Y.
(2002). Lymph node macrophages,
high levels of unmasked siaload-
hesin: implication for the adhesive
properties of macrophages in vivo.
Glycobiology 12, 209–216.
Nitschke, L., Carsetti, R., Ocker, B.,
Kohler, G., and Lamers, M. C.
(1997). CD22 is a negative regulator
of B-cell receptor signalling. Curr.
Biol. 7, 133–143.
Nitschke, L., Floyd, H., Ferguson, D. J.,
tion of CD22 ligands on bone mar-
row sinusoidal endothelium impli-
cated in CD22-dependent homing
of recirculating B cells. J. Exp. Med.
Nitschke, L., Lajaunias, F., Moll, T., Ho,
L., Martinez-Soria, E., Kikuchi, S.,
house, R. M., and Izui, S. (2006).
Expression of aberrant forms of
CD22 on B lymphocytes in Cd22a
lupus-prone mice affects ligand
binding. Int. Immunol. 18, 59–68.
O’Keefe, T. L., Williams, G. T., Batista,
F. D., and Neuberger, M. S. (1999).
Deficiency in CD22,a B cell-specific
inhibitory receptor, is sufficient to
predispose to development of high
affinity autoantibodies. J. Exp. Med.
O’Keefe, T. L., Williams, G. T., Davies,
S. L., and Neuberger, M. S. (1996).
Hyperresponsive B cells in CD22-
Onodera,T.,Poe,J. C.,Tedder,T. F.,and
Tsubata, T. (2008). CD22 regulates
time course of both B cell division
and antibody response. J. Immunol.
O’Reilly, M. K., Tian, H., and Paulson,
J. C. CD22 is a recycling receptor
that can shuttle cargo between the
ments of B cells. (2011). J. Immunol.
D.,Perlmutter,R. M.,Law,C. L.,and
Clark, E. A. (1996). CD22 regulates
thymus-independent responses and
the lifespan of B cells. Nature 384,
Otipoby,K. L.,Draves,K. E.,and Clark,
E. A. (2001). CD22 regulates B cell
receptor-mediated signals via two
domains that independently recruit
Grb2 and SHP-1. J. Biol. Chem. 276,
Pao, L. I., Lam, K. P., Henderson, J.
M., Kutok, J. L., Alimzhanov, M.,
G., and Rajewsky, K. (2007). B cell-
specific deletion of protein-tyrosine
phosphatase Shp1 promotes B-1a
cell development and causes sys-
temic autoimmunity. Immunity 27,
Patel, N., Brinkman-Van Der Linden,
E. C., Altmann, S. W., Gish, K.,
Balasubramanian, S., Timans, J. C.,
Peterson, D., Bell, M. P., Bazan, J.
F., Varki, A., and Kastelein, R. A.
(1999). OB-BP1/Siglec-6. A leptin-
and sialic acid-binding protein of
the immunoglobulin superfamily. J.
Biol. Chem. 274, 22729–22738.
Peaker, C. J., and Neuberger, M. S.
(1993). Association of CD22 with
the B cell antigen receptor. Eur. J.
Immunol. 23, 1358–1363.
Pillai, S., Cariappa,A., and Moran, S. T.
commitment during peripheral B-
Rev. 197, 206–218.
Poe, J. C., Fujimoto, Y., Hasegawa,
M., Haas, K. M., Miller, A. S.,
Sanford, I. G., Bock, C. B., Fuji-
moto, M., and Tedder, T. F. (2004).
January 2012 | Volume 2 | Article 96 | 13
Jellusova and NitschkeInhibitory Siglecs on B cells
CD22 regulates B lymphocyte func-
tion in vivo through both ligand-
dependent and ligand-independent
Powell, L. D., Sgroi, D., Sjoberg, E.
R., Stamenkovic, I., and Varki,
A. (1993). Natural ligands of the
B cell adhesion molecule CD22
with alpha-2,6-linked sialic acids
that are required for recognition. J.
Biol. Chem. 268, 7019–7027.
Neurochem. 100, 1431–1448.
Ramya, T. N., Weerapana, E., Liao,
L., Zeng, Y., Tateno, H., Yates, J.
R. III, Cravatt, B. F., and Paul-
son, J. C. (2010). In situ trans lig-
ands of CD22 identified by glycan-
proteomics. Mol. Cell. Proteomics 9,
Masking and unmasking of the
sialic acid-binding lectin activity of
CD22 (Siglec-2) on B lymphocytes.
Proc. Natl. Acad. Sci. U.S.A. 95,
Razi, N., and Varki, A. (1999). Cryp-
tic sialic acid binding lectins on
human blood leukocytes can be
unmasked by sialidase treatment or
cellular activation. Glycobiology 9,
Samardzic, T., Marinkovic, D., Danzer,
C. P., Gerlach, J., Nitschke, L., and
Wirth, T. (2002). Reduction of mar-
ginal zone B cells in CD22-deficient
mice. Eur. J. Immunol. 32, 561–567.
Santos, L., Draves, K. E., Boton, M.,
Grewal, P. K., Marth, J. D., and
Clark, E. A. (2008). Dendritic cell-
eration requires CD22. J. Immunol.
Sato, S., Miller, A. S., Inaoki, M., Bock,
C. B., Jansen, P. J., Tang, M. L., and
Tedder, T. F. (1996). CD22 is both
a positive and negative regulator of
B lymphocyte antigen receptor sig-
CD22-deficient mice. Immunity 5,
Sato, S., Tuscano, J. M., Inaoki, M., and
and positively regulates signal trans-
duction through the B lymphocyte
antigen receptor. Semin. Immunol.
Schadee-Eestermans, I. L., Hoefsmit, E.
C., Van De Ende, M., Crocker, P.
R., Van Den Berg, T. K., and Dijk-
stra, C. D. (2000). Ultrastructural
localisation of sialoadhesin (siglec-
1) on macrophages in rodent lym-
phoid tissues. Immunobiology 202,
Scharenberg, A. M., Humphries, L. A.,
and Rawlings, D. J. (2007). Calcium
signalling and cell-fate choice in B
G., Delogu, A., Busslinger, G. A.,
and Busslinger, M. (2007). Tran-
scription factor Pax5 activates the
chromatin of key genes involved in
Seite, J. F., Cornec, D., Renaudineau,
Y., Youinou, P., Mageed, R. A.,
and Hillion, S. (2010). IVIg modu-
lates BCR signaling through CD22
and promotes apoptosis in mature
human B lymphocytes. Blood 116,
Sgroi, D., Koretzky, G. A., and Sta-
menkovic, I. (1995). Regulation of
CD45 engagement by the B-cell
receptor CD22. Proc. Natl. Acad. Sci.
U.S.A. 92, 4026–4030.
Sjoberg, E. R., Powell, L. D., Klein, A.,
and Varki, A. (1994). Natural lig-
ands of the B cell adhesion molecule
CD22 beta can be masked by 9-O-
Smith, K. G., Tarlinton, D. M., Doody,
G. M., Hibbs, M. L., and Fearon, D.
T. (1998). Inhibition of the B cell by
CD22:a requirement for Lyn. J. Exp.
Med. 187, 807–811.
Stamatos, N. M., Curreli, S., Zella, D.,
of glycoconjugates on the surface of
signal-related kinases ERK 1/2 and
results in enhanced production of
Surolia, I., Pirnie, S. P., Chellappa, V.,
Taylor, K. N., Cariappa, A., Moya, J.,
Liu, H., Bell, D. W., Driscoll, D. R.,
Diederichs, S., Haider, K., Netravali,
I., Le, S., Elia, R., Dow, E., Lee, A.,
tien, Y., Varki, A., Macdonald, M.
E., Gillis, T., Behrens, T. W., Bloch,
D., Collier, D., Korzenik, J., Podol-
sky, D. K., Hafler, D., Murali, M.,
Sands, B., Stone, J. H., Gregersen, P.
defective germline variants of sialic
Nature 466, 243–247.
Takashima, S. (2008). Characteriza-
genes: their evolution and diver-
sity. Biosci. Biotechnol. Biochem. 72,
Tuscano, J. M., Riva, A., Toscano, S. N.,
Tedder,T. F.,and Kehrl,J. H. (1999).
CD22 cross-linking generates B-cell
antigen receptor-independent sig-
nals that activate the JNK/SAPK
Uckun, F. M., Goodman, P., Ma, H.,
Dibirdik, I., and Qazi, S. (2010).
CD22 EXON 12 deletion as a path-
ogenic mechanism of human B-
Sci. U.S.A. 107, 16852–16857.
Varki, A. (2009). Multiple changes
human evolution. Glycoconj. J. 26,
Glycobiology 16, 1R–27R.
Viglianti, G. A., Lau, C. M., Han-
ley, T. M., Miko, B. A., Shlomchik,
M. J., and Marshak-Rothstein, A.
(2003). Activation of autoreactive B
cells by CpG dsDNA. Immunity 19,
Waisman, A., Kraus, M., Seagal, J.,
Ghosh, S., Melamed, D., Song, J.,
bacher, F., Nitschke, L., and Rajew-
sky, K. (2007). IgG1 B cell recep-
tor signaling is inhibited by CD22
and promotes the development of B
on Ig alpha/beta. J. Exp. Med. 204,
Wakabayashi, C., Adachi, T., Wien-
ands, J., and Tsubata, T. (2002).
A distinct signaling pathway used
by the IgG-containing
Whitney, G., Wang, S., Chang, H.,
Cheng, K. Y., Lu, P., Zhou, X.
D., Yang, W. P., Mckinnon, M.,
and Longphre, M. (2001). A new
siglec family member, siglec-10, is
expressed in cells of the immune
system and has signaling properties
similar to CD33. Eur. J. Biochem.
Yohannan, J., Wienands, J., Cogge-
shall, K. M., and Justement, L.
B. (1999). Analysis of tyrosine
actions between stimulatory effec-
tor proteins and the B cell co-
receptor CD22. J. Biol. Chem. 274,
Zhang, J. Q., Biedermann, B., Nitschke,
L., and Crocker, P. R. (2004).
The murine inhibitory receptor
mSiglec-E is expressed broadly on
cells of the innate immune system
whereas mSiglec-F is restricted to
eosinophils. Eur. J. Immunol. 34,
Zhang, J. Q., Nicoll, G., Jones, C.,
and Crocker, P. R. (2000). Siglec-9,
a novel sialic acid binding mem-
ber of the immunoglobulin super-
family expressed broadly on human
blood leukocytes. J. Biol. Chem. 275,
Zhang, M.,Angata, T., Cho, J. Y., Miller,
M., Broide, D. H., and Varki, A.
of Siglec-F, a CD33-related Siglec
expressed on mouse eosinophils.
Blood 109, 4280–4287.
Zhang, M., and Varki, A. (2004). Cell
surface sialic acids do not affect pri-
mary CD22 interactions with CD45
and surface IgM nor the rate of con-
stitutive CD22 endocytosis. Glycobi-
ology 14, 939–949.
Conflict of Interest Statement: The
authors declare that the research was
conducted in the absence of any com-
mercial or financial relationships that
could be construed as a potential con-
flict of interest.
Received: 17 November 2011; paper
pending published: 12 December 2011;
accepted: 28 December 2011; published
online: 11 January 2012.
Citation: Jellusova J and Nitschke L
(2012) Regulation of B cell functions by
the sialic acid-binding receptors Siglec-
G and CD22. Front. Immun. 2:96. doi:
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Frontiers in Immunology | B Cell Biology
January 2012 | Volume 2 | Article 96 | 14