226
6 Immunoproteins
the laboratory mouse, but additional investigations have been carried out on other mammals.
All mammals appear to possess the five Ig classes
described, and IgG predominates in the blood
plasma even in the monotremes. The proportions
of the two L-chain types lot and A, which in man
are about 60:40, vary in the mammals over a very
wide range, from 95 % lot in the mouse to more
than 95 % A in the horse. Many mammals have Ig
subclasses and Ig isotypes that suggest the existence of multiple CH or CL genes; for example,
subclasses of IgG are detectable even in the marsupials [110].
In birds there are three, or perhaps four, Ig
classes, and in the remaining vertebrates there
are at the most two, which fall into two groups,
high molecular weight (HMW) and low molecular weight (LMW), according to their molecular
size. They are only partially comparable with the
Ig classes of the mammals. The HMWs found in
all non-mammals have sedimentation coefficients
of 16-19S and molecular masses of 720-920 kDa
and are very similar to IgM. The HMWs contain
H chains of 70-72 kDa and L chains of
23-25 kDa and are therefore polymers of the
basic Ig structural unit. Their structures can be
described by the formula (~Hz)n> where n may
have a value of 2, 4 or 5. Different degrees of
polymerization are found even in closely related
species. Thus, the ray Dasyatis centrura has an
HMW with n = 2, but in D. americana n = 5.
HMWs with n = 4, corresponding to about
720 kDa, are widely found in the bony fish, e.g.
in Lepisosteus, Polyodon, and many teleosts. The
teleost Archosargus probatocephalus has two
HMWs with n = 2 and n = 4 [138, 154]. The
chains of some immunoglobulins, e.g. the HMW
of the sea lamprey Petromyzon marinus and the
LMW of the frog Rana catesbeiana, can be separated without previous reduction and are therefore
apparently not linked by disulphide bridges.
The agnathans, cartilaginous fish and bony fish
usually contain only the HMW form. Some fish,
however, also possess LMW. In the case of many
shark species, these LMWs contain H chains of
the same size· and immunological character as
those of the HMW and are therefore, perhaps,
HMW monomers [154]. The ray Raja kenojei and
the other skates and rays may be considered as
the lowest vertebrates to have two well-defined Ig
classes. R. kenojei and other Rajidae possess pentameric HMWs with chains of 70 and 23 kDa as
well as dimeric LMWs with chains of 45-50 kDa
and 23 kDa [67]. The sharks Carcharhinus plumbeus and Heterodontus francisci have several CL
gene segments; the encoded amino acid sequen\ces are more similar (40 %) to the A chains of
mammals than to the lot chains [160, 165]. Wellcharacterized immunoglobulins of low molecular
mass are found in the anurans; the axolotl, a representative of the urodelans, has only HMW. The
LMWs of the anurans, reptiles and birds are more
similar to the mammalian IgA than to IgG; they
are often referred to as IgY [133]. In the chicken,
but also in the anuran Xenopus laevis, there are
three different CH gene segments [3, 133].
The Ig genes of all vertebrates from the agnathan and cartilaginous fish onwards are apparently formed by combination of V, (D), J and C
segments. In various teleosts and the clawed frog
Xenopus laevis, the variable Ig regions are
encoded, as in the mammals, by tandemly
arranged multiple V H, D and J gene segments
[4, 163]. Both membrane-bound and secretory
IgMs have been identified in the teleost Ictalurus
punctatus; however, !!M is markedly smaller than
!!s as a result of deviant splicing [198]. In Elasmobranchii, such as the horned shark Heterodontos francisci or the ray Raja erinacea, the Ig segments are arranged in a manner very different
from that in mammals, anurans and teleosts. In
this case, the Ig locus consists of many tandemly
arranged clusters with the structure VWDI-Dz-Jw
CH. The free combination of single gene segments
found in the mammalian system is thus excluded
and each variable segment VH-D1-DZ-JH is apparently assigned to a certain CH. The sequences of
the numerous CH segments are very varied
[67, 90]. If the birds are also taken into account,
then two quite different strategies for creating
antibody diversity are recognizable amongst the
vertebrates. In the Elasmobranchii, as in the
mammals, there is a large repertoire of V genes
available; at the A locus of the chicken, however,
there is only one single functional VA gene in addition to a h gene, but this is diversified by gene
conversion with about 25 available VA pseudogenes. In addition to this, the variety of L chains in
the chicken, as in the mammals, is increased by
somatic mutation and imprecise VJh linkage. As
a result of this process about 10 6 different antibodies are formed; this is only one order of magnitude less than in mammals [133]. The variety of
immunoglobulins in the lower vertebrates is much
less than that found in the mammals.
Following immunization with a low molecular
weight hapten like dinitrophenol, mice produce
about 500 different antibodies which are specific
for this antigen but are electrophoretically distinguishable (spectrotypes); the pattern varies
6 Immunoproteins
the laboratory mouse, but additional investigations have been carried out on other mammals.
All mammals appear to possess the five Ig classes
described, and IgG predominates in the blood
plasma even in the monotremes. The proportions
of the two L-chain types lot and A, which in man
are about 60:40, vary in the mammals over a very
wide range, from 95 % lot in the mouse to more
than 95 % A in the horse. Many mammals have Ig
subclasses and Ig isotypes that suggest the existence of multiple CH or CL genes; for example,
subclasses of IgG are detectable even in the marsupials [110].
In birds there are three, or perhaps four, Ig
classes, and in the remaining vertebrates there
are at the most two, which fall into two groups,
high molecular weight (HMW) and low molecular weight (LMW), according to their molecular
size. They are only partially comparable with the
Ig classes of the mammals. The HMWs found in
all non-mammals have sedimentation coefficients
of 16-19S and molecular masses of 720-920 kDa
and are very similar to IgM. The HMWs contain
H chains of 70-72 kDa and L chains of
23-25 kDa and are therefore polymers of the
basic Ig structural unit. Their structures can be
described by the formula (~Hz)n> where n may
have a value of 2, 4 or 5. Different degrees of
polymerization are found even in closely related
species. Thus, the ray Dasyatis centrura has an
HMW with n = 2, but in D. americana n = 5.
HMWs with n = 4, corresponding to about
720 kDa, are widely found in the bony fish, e.g.
in Lepisosteus, Polyodon, and many teleosts. The
teleost Archosargus probatocephalus has two
HMWs with n = 2 and n = 4 [138, 154]. The
chains of some immunoglobulins, e.g. the HMW
of the sea lamprey Petromyzon marinus and the
LMW of the frog Rana catesbeiana, can be separated without previous reduction and are therefore
apparently not linked by disulphide bridges.
The agnathans, cartilaginous fish and bony fish
usually contain only the HMW form. Some fish,
however, also possess LMW. In the case of many
shark species, these LMWs contain H chains of
the same size· and immunological character as
those of the HMW and are therefore, perhaps,
HMW monomers [154]. The ray Raja kenojei and
the other skates and rays may be considered as
the lowest vertebrates to have two well-defined Ig
classes. R. kenojei and other Rajidae possess pentameric HMWs with chains of 70 and 23 kDa as
well as dimeric LMWs with chains of 45-50 kDa
and 23 kDa [67]. The sharks Carcharhinus plumbeus and Heterodontus francisci have several CL
gene segments; the encoded amino acid sequen\ces are more similar (40 %) to the A chains of
mammals than to the lot chains [160, 165]. Wellcharacterized immunoglobulins of low molecular
mass are found in the anurans; the axolotl, a representative of the urodelans, has only HMW. The
LMWs of the anurans, reptiles and birds are more
similar to the mammalian IgA than to IgG; they
are often referred to as IgY [133]. In the chicken,
but also in the anuran Xenopus laevis, there are
three different CH gene segments [3, 133].
The Ig genes of all vertebrates from the agnathan and cartilaginous fish onwards are apparently formed by combination of V, (D), J and C
segments. In various teleosts and the clawed frog
Xenopus laevis, the variable Ig regions are
encoded, as in the mammals, by tandemly
arranged multiple V H, D and J gene segments
[4, 163]. Both membrane-bound and secretory
IgMs have been identified in the teleost Ictalurus
punctatus; however, !!M is markedly smaller than
!!s as a result of deviant splicing [198]. In Elasmobranchii, such as the horned shark Heterodontos francisci or the ray Raja erinacea, the Ig segments are arranged in a manner very different
from that in mammals, anurans and teleosts. In
this case, the Ig locus consists of many tandemly
arranged clusters with the structure VWDI-Dz-Jw
CH. The free combination of single gene segments
found in the mammalian system is thus excluded
and each variable segment VH-D1-DZ-JH is apparently assigned to a certain CH. The sequences of
the numerous CH segments are very varied
[67, 90]. If the birds are also taken into account,
then two quite different strategies for creating
antibody diversity are recognizable amongst the
vertebrates. In the Elasmobranchii, as in the
mammals, there is a large repertoire of V genes
available; at the A locus of the chicken, however,
there is only one single functional VA gene in addition to a h gene, but this is diversified by gene
conversion with about 25 available VA pseudogenes. In addition to this, the variety of L chains in
the chicken, as in the mammals, is increased by
somatic mutation and imprecise VJh linkage. As
a result of this process about 10 6 different antibodies are formed; this is only one order of magnitude less than in mammals [133]. The variety of
immunoglobulins in the lower vertebrates is much
less than that found in the mammals.
Following immunization with a low molecular
weight hapten like dinitrophenol, mice produce
about 500 different antibodies which are specific
for this antigen but are electrophoretically distinguishable (spectrotypes); the pattern varies