Page 1
This article appeared in a journal published by Elsevier. The attached
copy is furnished to the author for internal non-commercial research
and education use, including for instruction at the authors institution
and sharing with colleagues.
Other uses, including reproduction and distribution, or selling or
licensing copies, or posting to personal, institutional or third party
websites are prohibited.
In most cases authors are permitted to post their version of the
article (e.g. in Word or Tex form) to their personal website or
institutional repository. Authors requiring further information
regarding Elsevier’s archiving and manuscript policies are
encouraged to visit:
http://www.elsevier.com/copyright
Page 2
Author's personal copy
Immunobiology 216 (2011) 1318– 1321
Contents lists available at ScienceDirect
Immunobiology
j ourna l homepage: www.elsev ier .de / imbio
Review
“Natural” antibodies and histo-blood groups in biological development with
respect to histo-blood group A. A perspective review
Peter Arend ∗,1
a r t i c l e i n f o
Article history:
Received 14 November 2010
Accepted 24 April 2011
Keywords:
“Natural” antibody
Embryonic stem cells
Parthenogenesis
Neo-expression
a b s t r a c t
The “inappropriate” A-specific ovarian glycosphingolipids discovered in unfertilized C57BL/10J female
mice reflect growth processes, which suggest the activity of embryonic stem cells undergoing genetic
polymorphism. And the responding anti-GalNAc antibody represents the first classical “natural” anti-
body, which was unmasked as a highly specific autoantibody. This murine anti-A is subspecifically distinct
from the human antibody, discovering by a broader reactivity growth-dependent, xenoreactive A-specific
structures also in non-reproductive murine tissues, where an equivalent of the human AB gene family as
a cis AB-gene encodes A-and B glycotransferases. Expression of antigen is known to need always more
than its encoded enzyme, and the special mechanism which in the C57BL/10J murine ovarian glycosp-
ingolipids blocks the expression of “B” still remains still unknown. A herewith arising postulation of a
growth-predominating common biological activity may be supported by findings in rats. The number of
A-genes here significantly exceeds those of B and in the Wistar rat the A-antigen is only expressed in
the wild type, while B-expression requires the transfer of human B. Nevertheless in transgenic rats, the
appearance of “A” still remains more pronounced. The observations lead to reports on animals, which
do not show AB transferase production or a respective antigen expression in their normal tissues, but
inconcistently display A activity in malignant tumors. And respective examples are delivered by pheno-
type independent neo expressions of “inappropriate” A-specific structures in human cancer. Although in
comparison with epitope deletions they are rare, the ubiquitous “natural” (IgM and IgG) anti-A and anti-B
levels, against self and not self, irrespective of the blood group in any normal human sera, may reflect
invisible “inappropriate” A-specific growth. The role of the associated (auto) anti-B might be different,
because B-neo expressions obviously not occur in cancer, and anti-gal-antibodies are supposed to orig-
inate primarily from environmental, cross-reactive stimulation, and beyond their functions in defense
are otherwise engaged in physiology. In general natural antibody specificities undergo significant phy-
logenetical changes within the species. However, the in nature wide-spread “natural” anti-A agglutinin
specificities survived or even predominated the long-term evolution from the brown trout up to man and
still respond to the biological power, i.e. the products of a CAZY glycosyltransferase 6 (ABO) gene family.
It is so hypothesized that both, the murine and human “natural” anti-A antibodies represent examples
of a still to be analyzed polyclonal response to a provocative, species-independent evolutionary epi-
tope, which arises or escapes by some enzymatic predominance from the genetical polymorphism in a
consistent developmental process.
© 2011 Elsevier GmbH. All rights reserved.
A fortunate experimental condition was presented by the
anatomy of the C57BL/10J inbred mouse, where a particularly
endogenous origin of “natural” antibody production could be
demonstrated (Arend and Nijssen 1977a,b). The first time one
of the so-called “natural” antibodies was here unmasked as a
specific (auto) antibody, and growth processes were already pos-
∗ Corresponding author at: Am oberen Stötchen 14, - D-57462 Olpe - Germany.
Tel.: +49 2761 71963; fax: +49 2761 825156.
E-mail address: parend@t-online.de
1 Retired from: Research Laboratories Chemie Grünenthal, D-52099 Aachen -
Germany.
tulated (Arend and Nijssen 1977b). This observation appeared in
contrast to the previous concepts of a predominant environmen-
tal origin (Eisler 1930; Landsteiner 1931; Springer et al. 1961;
Springer and Horton 1969) and does not meet completely cur-
rent viewpoints of respective T- and B-cell involvements (Kyoko
et al. 1999; Marchalonis et al. 2001). But growth-dependent
“inappropriate” A-specific structures in the maturating ovary of
unfertilized females were clearly identified as the autologous
source of this “natural” antibody induction against the common,
by man and animals produced histo (blood) group antigen A
(Arend and Nijssen 1977a,b; Rocher 2005). So the appearance of
the anti-A hemagglutinin and complement-dependent hemolysin,
both of not yet determined protein and/or immunoglobulin classes,
0171-2985/$ – see front matter © 2011 Elsevier GmbH. All rights reserved.
doi:10.1016/j.imbio.2011.04.008
Page 3
Author's personal copy
P. Arend / Immunobiology 216 (2011) 1318– 1321 1319
was stopped by early ovariectomy, which together with the
organ apparently removed the A-specific autoantigenic power
(Arend and Nijssen 1977a).
The murine “natural” hemagglutinin and hemolysin, reacting
strongly with human blood group A erythrocytes, and differentiat-
ing between the subgroups A1 and A2, were inhibited exclusively by
autologous, water-soluble A-specific glycosphingolipids detected
in the ovary. In general, the inhibitory effects were modest, but
the data, obtained in prospectively designed and double-blind
performed experiments, could be saved at statistically significant
levels on the basis of multiple comparisons with 17 other male and
female tissues (Arend and Nijssen 1976, 1977a). Binding specifi-
cally the lectins of Helix pomatia and Dolichos biflorus (Arend and
Nijssen 1977b), they exhibit N-acetyl-d-galactosamine in a termi-
nal linkage, but are not yet further analyzed on a current chemical
and genetical basis. Markedly age-dependent, they reach their peak
of activity at the onset of puberty (Arend and Nijssen, 1977a,b) and
did not show any A-specific expression at birth. Their production
always precedes the appearance of their corresponding antibody,
which was demonstrated at extremely low levels, if at all, in
early ovariectomized animals. Its auto-reactive hemagglutinin and
hemolysin specificities do not include Forssman reactivity and were
shown to be distinct from the human anti-A antibody, which by
broader subspecificities detects growth-dependent, xeno-reactive
A-like structures in several other murine tissues (Arend 1979).
Moreover, there is no comparable murine anti-B antibody of
endogenous origin (Néron and Lemieu, 1994). While an anti-B can
be exogenously induced in the C57BL/10J inbred mouse by the
B-reactive lipopolysaccharide of Escherichia coli O86, it is always
associated with a cross-reactive immune anti-A, which together
with the immune anti-B can be absorbed by the microbial anti-
gen and separated from the endogenous, “natural” anti-A antibody
(Arend 1971). So the essentially different inductive sources and
antibody specificities, i.e. the endogenously induced anti-GalNAc�-
and exogenously stimulated anti-galactosyl, exhibit themselves
within a “natural” antibody repertoire, which in such constella-
tions does never spontaneously occur in mice, however became
important in human immunobiology. Because here “naturally”
occurring anti-�-galactosyl antibodies, beyond their functions in
defense, display various specificities and are probably otherwise
engaged in physiology. Most abundant and widely studied are the
anti-Gal�1,3Gal antibodies, which are heterogeneous in terms of
subspecificities. For instance, the unique “natural” IgG antibody
exhibiting anti-Gal�3Gal�4GlcNAc specificity, which is present in
any human serum in high concentrations (Galili et al. 1984) and sig-
nificantly reactive with senescent blood cells, obviously plays a role
in age processes and becomes important in studying the phyloge-
nesis of serologically relevant carbohydrates. Another new species
of human “natural” anti-galactosyl antibodies and distinct from the
Galili antibody, is represented by the anti-NOR, detecting the rare
Gal�-1-4GalNAc (NOR) antigen, also reactive with the lectin of Grif-
fonia simplicifolia IB4 (Duk et al. 2003). Its role, however in human
physiology still awaits elucidation.
Today it is widely accepted that “natural” antibodies reflect a
variety of origins (Baumgarth et al. 2005) and are believed to be
produced even without any exogenous stimulation, but neverthe-
less are polyreactive with self and not self structures and so are
always (auto)-antibodies as well (Casali and Schettino 1996; Cheng
and Chamley 2008). Their appearance in healthy man and ani-
mals in general excludes autoimmune diseases. Moreover, their
interaction with cell surface structures initiates a series of intra-
cellular signalling events and leads to the release of membrane
molecules and over the time to suppression of cell proliferation in
both physiological and pathological conditions (Wang and Chow
2000). This process might be related to the observation where
“natural” antibodies sustain the differentiation and maturation of
human dendritic cells and could provide a biological mechanism
for direct control of activated cells (Jagadeesh et al. 2004). Finally,
with respect to the ABO histo-(blood group) antigen system the dis-
covery of the phenotype independent anti-A and anti-B (IgM and
IgG) antibodies may argue even against the hypothesis that “natu-
ral” alloreactive antibodies exhibit the characteristics of immune
antibodies that would result as a response to foreign A and B
substances of microorganisms. These immunglobulins purified by
affinity chromatography are reactive in the micromolar range with
A and B specific trisaccharides of autologous blood cells and are
apparently not controlled by the thymus but peripheral mecha-
nisms in normal human sera (Spalter et al. 1999). And “natural”
antibodies more and more appear to be involved in self control
procedures and to represent parts of a functional unity.
The particular association, or cooperation of specific surface
receptors with their corresponding (auto) antibody, may raise again
the old question, how the genetic background, when identified by
cell surface properties, could be of significance in disease and sur-
vival, i.e. evolutionary advantage. Cancer biology here is a large
field of discussion, and blood groups as genetic markers always
played a role. The molecular structures of the histo-blood type
ABH, Lewis, Tn and related systems, residing from fishes over snails
(Uhlenbruck et al. 1975) to mammals, in a long-term evolution of
the CAZY glycosyltransferase 6 (ABO) gene family (Turcot-Dubois
et al. 2007), were a matter of extensive experiments (Hakomori
1985). And the discovery of the A-related Tn structures and deriva-
tives as diagnostic markers and vaccines in tumor therapy and
prophylaxis was one of the first important results (Lo-Man et al.
2001).
But for various reasons, as probably not always comparable
investigative tools and the definition of phenotypes and sub-
groups, which in addition may change their expression during the
life, statistics about direct correlations between cancer and blood
groups were up to now not satisfying. So such correlations are still
questionable. While earlier reports appeared to reveal a modest
predominance for malignant growth in people with the expression
of blood group A, especially concerning certain organs such as the
ovary and intestinal tract, meanwhile too many discrepant results
do not permit final statistical inferences (data not shown). And
the latest prospective study, considering epithelial ovarian cancer,
demonstrated even a predominance of “B” instead of “A” (Gates et
al. 2011). Moreover, in an earlier report on blood group A patients,
suffering from non-small-cell cancer of the lung, the preservation
or appearance of A-like structures in the tumor cells was shown to
be even a favorable factor in prognosis (Lee et al. 1991).
However, although a disadvantage could so up to now not be
verified for the special expression of the histo-(blood group) A phe-
notype, which is based on a structure undergoing various changes
during tissue maturation and aging (Hakomori 1999), on the other
hand, irrespective from phenotype and species, A-specific struc-
tures appearing as evolutionary potentials probably dominate to
some extent growth processes per se. They obviously become in
sight in early development, as by the over-expressed “inappropri-
ate” A-specific ovarian glycosphingolipids in germ cell evolution of
C57BL/10J unfertilized inbred females. It appears intriguing that
here the lectin of Dolichos Biflorus, crucial in the reproductive
process of a higher plant, combines with “inappropriate” ovarian
glycosphingolipids in mammals (Arend and Nijssen 1977b) and sig-
nalizes A-determining N-acetyl-d-galactosamine epitopes on the
surface of active embryonic stem cells (Nash et al. 2007). These
observations are leading to reports on animals, which normally
do not show AB transferase production or a respective antigen
expression in any of their organs, but nevertheless may display
for up to now unknown genetical mechanims occasionally “inap-
propriate” A-activity in malignant tumors of non-reproductive
tissues (Hirota et al. 1992a) either spontaneously, or in response
Page 4
Author's personal copy
1320 P. Arend / Immunobiology 216 (2011) 1318– 1321
to chemical or pharmacological treatment (Hirota et al. 1992b).
And phenotype-independent neo-expressions of “inappropriate”
A-specific structures are also observed inconsistently in human
cancer, in tumors of blood group O (Clausen et al. 1986; Okada
et al. 1987; Metoki et al. 1989; David et al. 1993) as well as
in blood group B people (Hakomori 1999), while there is up to
now only one report on “inappropriate” B expression, occurring
however in cholangitis (Bloom et al. 1993). In comparison with var-
ious epitope deletions neo-expressions are relatively rare, but the
phenotype independent, ubiquitous anti A-antibody levels of sev-
eral immunoglobulin classes in normal human sera (Spalter et al.
1999) may primarily reflect an invisible “inappropriate” A-specific
growth. The role of the associated (auto) reactive anti-B might be
different. Cross-reactivity and environmental stimulation cannot
be excluded, but the above, although weak information of a lesser
pronounced developmental, “inappropriate” activity of the B gene
gets support again from further reports about rodents.
In fact, in rats the number of A-glycotransferase encoding genes
considerably exceeds that for B (Iwamato et al. 2002; Turcot
et al. 2003), and in the Wistar rat only the wild type exhibits
A-expression, whereas the expression of “B” requires the trans-
fer of the respective human genes. However, even in transgenic
animals, A-expression still remains pronounced (Iwamato et al.
2002). In mice the equivalent of the human ABO gene prevails
as a cis-AB gene and encodes a glycosyltransferase with both, A
and B transferase activities, but with special experimental tools
required for final antigen expression, “A” always becomes more
apparent than “B” (Yamamoto et al. 2001). So apart from the
exclusively over-expressed “inappropriate” A-specificity in ovar-
ian glycosphingolipids in the C57BL/10J female, expression of the A-
and B-antigens in the mouse clearly needs more than the encoded
enzyme. And it was suggested that this phenomenon of the more
apparent “A” partially may partially reside in substrate competition
between the more “bulky” N-acetyl-D-galactosamine molecule in
comparison with d-galactose (Yamamoto et al. 2001). So after all,
with respect to the number of A-transferase encoding genes as well
as from the molecular point of view the histo-(blood group) anti-
gen A might represent an example of an in development leading
structure, which by changing expressions demonstrates some great
polymorphic dynamics. The physiological relevance might reside
here, which in conclusion becomes evident by the immunologically
highly responded, provocative over-expression of “inappropriate
A-activity, due to aberrant A-glycotransferases in the maturat-
ing ovary of unfertilized C57BL/10J females (Arend and Nijssen
1976, 1977a,b), where parthenogenetical developmental processes
in unfertilized eggs are strongly suggested.
The reproductive pressure of inbreeding apparently promotes
parthenogenesis (Uyenoyama 1985). Increased developmental
potentials were already observed after pharmacological or hor-
monal manipulations respectively, particularly in inbred mice
(Downs 1990). And even viable chimaeras were already produced
from normal and parthenogenetic mouse embryos (Stevens et al.
1977). These studies perhaps also explain the observations in the
C57BL/10J female mouse, where the distribution of its growth
dependent xeno- and auto-reactive structures, could indeed
reflect the developmental process of tissue maturation during
ontogeny.
In man parthenogenetic potentials were recognized to be essen-
tial in stem cell research (Isaev et al. 2001; Kim et al. 2007; Polak de
Fried et al. 2008) and may be of significance in “natural” immunity
as well. But they are neither restricted to germinal tissue nor al ways
concentrated or over-expressed as in the ovary of the C57BL/10J
inbred mouse, discovered as experimental tool. During matura-
tion various potentials are preserved to some somatic cells, which
dependent from the kind of tissue, display different amounts and
qualities.
The human pluripotent, self-renewing cell dictates the devel-
opmental procedures in non reproductive tissue, but undergoes
genetical polymorphisms involving appearance of aberrant gly-
cotransferase specificities, i.e. the production of “inappropriate”
neo-antigens, for instance, such as “A”, the probably essential
source of induction of the classical anti-A antibody.
In general, “natural” antibody specificities undergo significant
phylogenetical changes against self and not self within the species
(Gonzalez et al. 1988). But the “natural” anti-A agglutinins sur-
vived or even predominated the long-term evolution from the
brown trout (Holt and Anstee 1975) up to man and respond
to the biological power of a CAZY glycosyltransferase 6 (ABO)
gene family (Turcot-Dubois et al. 2007). It is so hypothesized that
both, the murine and human “natural” anti-A antibodies represent
examples of a still to be analyzed polyclonal response to a species-
independent evolutionary epitope, which arises or escapes by some
enzymatic predominance from the genetical polymorphism in a
consistent developmental process.
References
Arend, P., 1971. Observations on different origins of “naturally” occurring antibodies.
European Journal of Immunology 5, 398–402.
Arend, P., Nijssen, J., 1976. Significance of specific ovarian receptors for syngeneic
naturally-occurring haemagglutinating anti-A antibodies. Journal of Immuno-
genetics 3, 373–382.
Arend, P., Nijssen, J., 1977a. Age-dependent appearance of A-specific ovarian gly-
colipids and syngeneic “natural” anti-A hemolysin in mice. Zeitschrift fur
Immunitatsforschung. Immunobiology 153, 74–84.
Arend, P., Nijssen, J., 1977b. A-specific autoantigenic ovarian glycolipids inducing
production of “natural” anti-A antibody. Nature 269, 255–257.
Arend, P., 1979. An auto-reactive A-like ovarian determinant distinct from xeno-
reactive A-like structures. Immunobiology 156, 410–417.
Baumgarth, Nicole, et al., 2005. Inherent specificities in natural antibodies, a
key to immune defense against pathogen invasion. Springer Seminars in
Immunopathology 26, 347–362.
Bloom, S., et al., 1993. Inappropriate expression of blood group antigens on biliary
and colonic epithelia in primary sclerosing cholangitis. Gut 34, 977–983.
Casali, P., Schettino, E., 1996. Structure and function of natural antibodies. Current
Topics in Microbiology and Immunology 210, 167–179.
Cheng, H., Chamley, L., 2008. Cryptic natural autoantibodies and co-potentiators.
Autoimmunity Reviews 7, 431–434.
Clausen, H., et al., 1986. Incompatible A antigen expressed in tumors of blood group
O individuals: immunochemical, immunohistologic and enzymatic characteri-
zation. The Journal of Immunology 136, 326–330.
David, Leonor, et al., 1993. Biosynthetic basis of incompatible histo-blood group A
antigen expression: anti-A transferase antibodies reactive with gastric cancer
tissue of type O individuals. Cancer Research 53, 494–5500.
Downs, S.M., 1990. Stimulation of parthenogenesis in mouse ovarian follicles by
inhibitors of inosine monophosphate dehydrogenase. Biology of Reproduction
43, 426–437.
Duk, M., et al., 2003. Specificity of human anti-NOR antibodies, a distinct species of
“natural” anti-galactosyl antibodies. Glycobiology 13, 279–284.
Eisler, M., 1930. Über ein gemeinsames Antigen in den Zellen des Menschen und in
Shiga-Bazillen. Zeitschrift fur Immunitatsforschung. Immunobiology 67, 38–49.
Gates, M.A., et al., 2011. ABO blood group and incidence of epithelial ovarian cancer.
International Journal of Cancer 128 (2), 482–486.
Galili, U., et al., 1984. A unique natural human IgG antibody with anti-�-galactosyl
specificity. Journal of Experimental Medicine 160, 1519–2153.
Gonzalez, R., et al., 1988. Specificity of natural serum antibodies present in phylo-
genetically distinct fish species. Immunology 63, 31–36.
Hakomori, S., 1985. Aberrant glycosylation in cancer cell membranes as focused on
glycolipids: overview and perspectives. Cancer Research 45, 2405–2414.
Hakomori, S., 1999. Antigen structure and genetic basis of histo-blood groups A, B
and O: their changes associated with human cancer. Biochimica et Biophysica
Acta 1473, 247–266.
Hirota, M., et al., 1992a. Purification and analysis of glycoproteins bearing blood
group-A determinants from hamster pancreatic ductal adenocarcinomas. Can-
cerogenesis 13, 1829–1833.
Hirota, M., et al., 1992b. Modification of blood group A antigen expression in a pan-
creatic cancer cell line (PC-1) by inhibitors of N-glycan processing. Journal of
Cellular Biochemistry, 13–20.
Holt, P.D.J., Anstee, D.J., 1975. A natural Anti-A agglutinin in the serum of the brown
trout (Salmo trutta). Vox Sanguinis 29, 286–291.
Isaev, D.A., et al., 2001. Different influences of genomic imprinting on the develop-
ment of parthenogenetic cell clones in C57BL/6 and CBA mice. Russian Journal
of Developmental Biology 32, 292–297.
Iwamato, S., et al., 2002. Rat encodes the paralogous gene equivalent of the human
histo-blood group ABO gene, association with antigen expression by over-
Page 5
Author's personal copy
P. Arend / Immunobiology 216 (2011) 1318– 1321 1321
expression of human ABO transferase. Journal of Biological Chemistry 277,
46463–46469.
Jagadeesh, B., et al., 2004. Natural antibodies sustain differentiation and maturation
of human dendritic cells. PNAS 101, 14210–14215.
Kim, K., et al., 2007. Recombination signatures distinguish embryonic stem cells
derived by parthenogenesis and somatic cell nuclear transfer. Cell Stem Cell 1,
346–352.
Kyoko, H., et al., 1999. Positive selection of natural autoreactive B cells. Science 285,
113–116.
Landsteiner, K., 1931. Individual differences in human blood. Science 73, 403–409.
Lee, J.S., et al., 1991. Expression of blood-group antigen A — a favorable prognos-
tic factor in non-small-cell lung cancer. New England Journal of Medicine 324,
1084–1090.
Lo-Man, R., et al., 2001. Anti-tumor immunity provided by a synthetic multiple anti-
genic glycopeptide displaying a Tri-Tn glycotope. The Journal of Immunology
166, 2849–2854.
Marchalonis, J., et al., 2001. Evolutionary factors in the emergence of the combi-
natorial germline antibody repertoire. Advances in Experimental Medicine and
Biology 484, 13–30.
Metoki, R., et al., 1989. Deletion of histo-blood group A and B antigens and expres-
sion of incompatible A antigen in ovarian cancer. Journal of the National Cancer
Institute 15, 1151–1157.
Nash, R., et al., 2007. The lectin Dolichos biflorus agglutinin recognizes gly-
can epitopes on the surface of murine embryonic stem cells: a new tool
for characterizing pluripotent cells and early differentiation. Stem Cells 4,
974–982.
Néron, S., Lemieu, R., 1994. Type 2 T-cell-independent murine immune response to
the human AB0 blood group antigens. Vox Sanguinis 67, 68–74.
Okada, Y., et al., 1987. Neoexpression of ABH and Lewis blood group antigens in
human hepatocellular carcinomas. Journal of the National Cancer Institute 1,
19–28.
Polak de Fried, E., et al., 2008. Human parthenogenetic blastocysts derived from non-
inseminated cryopreserved human oocytes. Fertility and Sterility 89, 943–947.
Rocher, J., 2005. Dévelopement de modèles expérimentaux envue de la mise au point
de protocoles d’immunothérapie ciblant les antigènes glycanniques sialyl-Tn et
A type ¾, antigènes associés aux carcinomes. Ecole Pratique des Hautes Etudes
(Sciences de la Vie et de la Terre), Diplomé.
Spalter, S.H., et al., 1999. Normal human serum contains natural antibodies reactive
with autologous ABO blood group antigens. Blood 93, 4418–4424.
Springer, G.F., et al., 1961. Blood group activity of gram negative bacteria. Journal of
Experimental Medicine 113, 1077–1093.
Springer, G.F., Horton, R.E., 1969. Blood group isoantibody stimulation in man
by feeding blood group-active bacteria. Journal of Clinical Investigation 48,
1280–1291.
Stevens, L.C., et al., 1977. Viable chimaeras produced from normal and partheno-
genetic mouse embryos. Nature 269, 515–517.
Turcot, A.L., et al., 2003. Cloning of a rat gene encoding the histo-blood group B
enzyme: rats have more than one Abo gene. Glycobiology 12, 919–928.
Turcot-Dubois, A.L., et al., 2007. Long-term evolution of the CAZY glycosyltransferase
6 (ABO) gene family from fishes to mammals, a birth-and-death evolution model.
Glycobiology 17, 516–528.
Uhlenbruck, G., et al., 1975. Blood group like substances in some marine inver-
tebrates. Different forms of the blood group A-like substances: glycoprotein
and polysaccharide type. Comparative Biochemistry and Physiology. Part B:
Biochemistry and Molecular Biology 50, 369–372.
Uyenoyama, M., 1985. On the evolution of parthenogenesis. II. Inbreeding and the
cost of meiosis. Evolution 39, 1194–1206.
Wang, H., Chow, D.A., 2000. Natural antibody-induced intracellular signalling and
growth control in C3H 10T1/2 fibroblast variants. Immunology 4, 458–466.
Yamamoto, M., et al., 2001. Murine equivalent of the human histo-blood group
ABO gene is a cis-AB gene and encodes a glycosyltransferase with both A and B
transferase activity. Journal of Biological Chemistry 276, 13701–13708.
