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Structural and genetic studies on chicken 7S immunoglobulin allotypes. II. Distribution of allotypes on the 7S immunoglobulin of homozygous and heterozygous chickens.

We have previously reported that chicken 7S immunoglobulin (Ig) heavy (H) chain allotypes (CS-1 locus) segregate as phenogroups in F2 progeny. Specificity CS-1.1 formed a phenogroup with CS-1.4 in inbred chicken line UCD 2, and a second phenogroup with CS-1.3 in line UCD 3. To determine whether these phenogroups were formed by combinations of specificities on the same, or on separate subclasses of 7S Ig, their distribution on the 7S Ig molecules of birds homozygous for 7S Ig allotypes was analyzed by radioimmunoassay. Anti-CS-1.1 and anti-CS-1.3 alloantisera each bound more than 94% of line UCD 3 1252-7S Ig. Similar results were obtained with alloantisera to CS-1.1 and CS-1.4 WITH 125 I-7S Ig from line UCD 2. These results indicate that both phenogroups were formed by combinations of specificities present on the same H chain. Thus, each phenogroup described, probably is the product of a single structural gene which is responsible for more than 94% of the 7S Ig H chain constant regions. In F hybrids with the genotype CS-1.3, 1.3/CS-1.2, two populations of serum 7S Ig molecules were detected by direct and sequential binding analysis with specific alloantisera. One population of 7S Ig contained specificities CS-1.1 AND CS-1.3, but not CS-1.2; while the second population was exclusively the product of one parental allele. Consistent with a genetic regulatory mechanism involving allelic exclusion, no MS Ig containing allotypes produced by both alleles was detected.

Animals

Structural and genetic studies on chicken 7S immunoglobulin allotypes. IV. The presence of an unexpected chicken immunoglobulin heavy chain allotype: subclass or pseudoallele?

Low concentrations of allotypic specificity CS-1.1 were detected in the sera of two inbred chicken lines [University of California, Davis (UCD) 7 and Regional Poultry Research Laboratory 15I4] previously reported to lack this specificity. The CS-1.1 alloantigen in 15I4 chickens has the same specificity as the major allotype in a line of chickens (UCD 2) in which it was initially defined. In 15I4 chickens, CS-1.1 allotype is present on a population of molecules distinct from those which carry the major allotype; thus a second 7S Ig H chain locus, CS-2, is proposed. The concentration of CS-1.1-bearing molecules determined by two different methods was 7 microgram/ml and 230 microgram/ml in 15I4, whereas UCD 2 chickens had 4 mg/ml of CS-1.1 molecules. The levels of CS-1.1 inhibitory activity in 15I4 birds remained relatively constant over a 30-day period. The presence of two 7S Ig populations in 15I4 chickens may be interpreted as evidence either for 7S Ig subclasses with shared allotypes or for a pseudoallelic organization of genes controlling expression of 7S Ig H chains. The results were consistent with the presence of redundant C region genes, differing in allotypes, whose expression is under the control of an as yet undefined regulatory mechanism.

Alleles

Surface immunolglobulin on rabbit lymphoid cells. VI. Failure to detect d and e group immunoglobulin allotypes on lymphocytes by immunoelectron microscopic labeling.

Surface immunoglobulin allotypes on rabbit peripheral blood lymphocytes (PBL) and spleen lymphocytes are detected by an immunoferritin labeling technique for electron microscopy. Human red blood cells, chemically coated with purified rabbit IgG of specific allotypes, served as test cells to assess the labeling specificity and efficiency. Immunoelectron microscopic labeling reveals that groups a, b, d and e allotypic specificities are readily detectable on passively coated test cells. However, only a and b group markers are detectable on lymphocytes. On rabbit PBL both a (VH of Fd region) and b (kappa chain constant region) group allotypes are detectable (73-78% and 68-77%, respectively); on spleen cells, 46% and 52-55% are positive for a and b locus allotypes, respectively. The d and e allotypes (i. e. gamma chain-specific) are undetectable on PBL or on spleen lymphocytes using this method. We conclude that the d and e group allotypes are either not present on the lymphocyte surface or are buried in the surface membrane and unacessible to the antisera used in this immunoferritin labeling technique.

Animals

A search for association between IgD concentrations and immunoglobulin allotypes in 936 sera from a genetic isolate in Newfoundland.

Immunoglobulin allotype (Gm) data has been analysed agaonst immunoglobulin D (IgD) concentrations in a population study in Newfoundland. There was no significant difference between the distribution of IgD concentrations in people homozygous for the alleles G1m(f) and G3m(b) when compared with people homozygous for the alleles G1m(a) and G3m(g). These findings, involving 573 homozygous individuals as opposed to ninety-eight in an earlier study on a New York population, do not confirm the earlier findings. Thus a genetic influence on IgD concentration by Gm genes or genes closely linked to them is not universally demonstrable by typing for these four markers and by using the Mancini technique for mearusing IgD concentration.

Gene Frequency

Quantitative analysis of spleen cell and immunoglobulin allotype composition of (CBAxCBA/H-T6) in equilibrium C57BL/6 allophenic mice.

Fifteen (CBAxCBA/H-T6) in equilibrium C57BL/6 allophenic mice were analyzed for the parental composition of their spleen white blood cells and serum immunoglobulin allotypes. The spleen compositions, assessed by a microcytotoxicity test, showed that the animals covered a range of parental cell mixtures. The allotype compositions of the IgG2a and IgG2b subclasses were determined by a solid phase radioimmunoassay. Although the absolute amount of IgG2a and IgG2b varied markedly from animal to animal, the percentage of the two allotypes in each subclass was remarkably constant. This suggests that the synthesis of IgG2a and IgG2b may be under a coordinate control system. Also, the spleen cell compositons were in excellent agreement with both the IgG2a and IgG2b subclass compositions. The quantitative analysis of the immune systems of allophenic mice may be first step toward the understanding of the mechanisms of tolerance of histoincompatible cells in allophenic mice.

Animals

Immunoglobulin allotypes in African populations. I. Gm--Am haplotypes in a Nigerian population.

The study of immunoglobulin allotypes in various Negro populations has shown that their polymorphism is different from that in other populations. This particularly true for the alleles of the gamma3 and alpha2 locus. Numerous investigations have been made in which a limited number of markers were determined. It seems to be of importance to compare the results of the determination of all markers known at present in different tribes from various African countries. Such information may ultimately lead to additional support for theories on the origin and migration of early African inhabitants. In this paper we resent the results of the study of the first of a series of studies on African populations.

Black People

The immunoglobulin allotypes (Gm and Km) of twelve Indian tribes of Central and South America.

The Gm and Km immunoglobulin allotypes are presented, for the first time, for six South American Indian tribes (Baniwa, Kanamari, Kraho, Makiritare, Panoa, and Ticuna) and one Central American tribe (Guaymi). Additional allotype information is presented for five previously reported South American tribes (Cayapo, Piaroa, Trio, Xavante and Yanomama). The distributions of the Gm and Km allotypes among all the tribal populations tested to date are reviewed and evidence is presented for the presence of a north (high)-south(low) cline in Km frequency. The wave theory of the populating of the South American continent was tested by an examination of the distribution of six alleles (Gmax;g, Gma;b0,3,t,Dia,Rx,TFDChi, and 6PGDC), absent in some populations but with polymorphic proportions in others. The present, limited, data failed to confirm the theory.

Alleles

Syngeneic lines of chickens. VI. Immunoglobulin allotypes.

In the course of study of alloantigenic immunoglobulin polymorphisms in 10 inbred chicken lines we detected 7 IgG allotypic specificities and 3 IgM allotypes. All birds in a given line possessed a unique combination of several IgG alloantigenic specificities (forming the phenogroup) which is presumably controlled by one allele at the locus designated a. We found five such phenogroups and five corresponding alleles (allele ac in three C lines, aI in three I lines, aW in two W lines, aM in line M, and aF in line F) in inbred lines tested. Furthermore, it could be inferred that each IgM allotype is the marker of one allele at the locus D. The distribution of these alleles among inbred lines was determined (allele dC was present in lines C and F, allele dI in lines I and M, and allele dW in lines W). A 2.8% recombination between loci a and d that are linked was found. The study of linkage between immunoglobulin allotype loci and blood group loci A, E, B, C, D, and I revealed no deviation from independent assortment of thse loci.

Animals

Structural and genetic studies on chicken 7S immunoglobulin allotypes. I. Detection of four heavy chain specificities with a new radioimmunoassay.

A method was developed for the detection of allotypes on intact, radiolabeled 7S immunoglobulin (Ig) which does not involve insolubilized alloantisera. Binding of dinitrophenylated anti-allotype (DAA) antiserum with radiolabeled alloantigen was demonstrated by the addition of rabbit anti-dinitrophenyl antiserum followed by precipitation of complexes with sheep anti-rabbit gamma-globulin antiserum. Dinitrophenylation of alloantiserum up to 8.5 hr had no effect on antibody titer or avidity. Binding inhibition assays with the DAA method detected allotypes on 2 to 5 ng of 7S Ig. Four specificities were detected on 7S Ig heavy (H) chains by binding inhibition with the DAA assay. Specificities CS-1.1 and CS-1.2, located in the Fab fragment, were detected at 3- to 5-fold lower concentrations of reassociated H and light (L) chains than on the isolated H chains. On the basis of regression coefficients calculated from binding inhibition curves, the avidity of isolated H chains was significantly increased following reassociation with L chains, indicating that the conformation of CS-1.1 and CS-1.2 determinants depends in part on H and L chain interactions. In contrast, reassociation of H and L chains did not significantly increase H chain inhibitory activity or avidity for specificities CS-1.3 and CS-1.4.

Animals

Immunoglobulin allotypes of rabbit kappa chains: polymorphism of a control mechanism regulating closely linked duplicated genes?

The amino acid sequence of the constant (CK) region from the kappa immunoglobulin chains of a b9 rabbit is compared with the CK sequences, taken from the literature, of a b4 rabbit. These CK regions differ by 33% of their amino acid sequences and by three sequence insertions or deletions (sequence gaps). These extensive differences together with other published observations suggest that the b9 and b4 CK genes may not be simple alleles, but rather they may be encoded by closely linked CK genes present in every rabbit whose expression is regulated by a polymorphic control mechanism.

Alleles

Structural and genetic studies on chicken 7S immunoglobulin allotypes. III. Proposed nomenclature for the CS-1 gene alleles.

A survey of 47 inbred or partially inbred chicken lines derived from five sources in the United States and Europe revealed considerable genetic polymorphism in the structural gene (CS-1) responsible for the production of the predominant chicken 7S Ig heavy chain. A minimum of 10 alleles of the CS-1 gene were detected as unique combinations or phenogroups of CS-1 specificities. A system of nomenclature for CS-1 alleles was developed and six homozygous lines were designated as prototype lines. The remaining four CS-1 alleles occurred only in lines that were polymorphic for 7S Ig allotypic specificities.

Alleles