<i>BASILEA</i> KAPPA LIGHT CHAINS OF RABBIT IMMUNOGLOBULINS

Dubiski, S.; Charpentier, L.; D’Agostaro, Giacomo

doi:10.1111/j.1744-313x.1982.tb00977.x

Cited by 8 publications

(2 citation statements)

References 13 publications

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“…To our knowledge, suppression of the ~2 isotype in Basilea rabbits has so far been done in the context of studies of rabbit light chains (Dubiski et al, 1982). In such bas suppressed rabbits auto-antibodies against ~2 could be raised which detected the K2 chain in homozygous d-suppressed rabbits using this isotype as one of the compensatory light chain for their loss of KI (Catty et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

In Utero Suppression of K2 Isotype in Homozygous Bas/Bas Rabbits Through Embryo Transfer

Meier¹,

Kelus²

1992

Int J Immunogenetics

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Allotypes of rabbit Ig provide a useful tool for the study of quantitative expression of alternative allelic forms. In the rabbit, maternal Ig is transmitted to the foetus and protects the immunologically immature newborn during several of the first weeks of life. Induced maternal antibodies directed towards a paternally inherited allotype of the offspring can influence the expression of that allotype drastically. Normal Ig level in heterozygous allotype suppressed animals is provided by increased expression of the alternative allele. On the other hand, allotype suppression in homozygous animals leads to increased expression of non-allelic alternative gene products. We quantitatively analysed the expression of bas, a marker on the kappa 2 light chain isotype of the mutant strain Basilea, in homozygous bas/bas rabbits which had been fostered in utero of b4/b6 mothers producing anti-bas. All of the offspring studied expressed the kappa 2 isotype at a very low level at two months of age, and, in some individuals, bas was hardly expressed after 6 to 12 months. A suppressed rabbit, which was immunized to produce auto-antibodies against bas, continued to do so for at least 2.5 years. The long duration of homozygous bas suppression contrasts with homozygous suppression of other allotypes (CL kappa 1 and VHa) which generally lasts for a much shorter period.

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Section: Discussionmentioning

confidence: 99%

In Utero Suppression of K2 Isotype in Homozygous Bas/Bas Rabbits Through Embryo Transfer

Meier¹,

Kelus²

1992

Int J Immunogenetics

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“…This report describes our investigations of the molecular basis for the loss of expression of K1 chains in the Basilea mutant.Rabbits are unusual in that they have two constant region r chain (C,) 1 genes (4, 5, 14-16). Although they have not yet been physically linked (4), the ~1 and ~2 genes are transmitted as linked traits in breeding colonies, and thus far no recombinants have been observed (6,7,(9)(10)(11). The rl and r2 genes each have their own J (joining region) clusters (3,5,15).…”

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confidence: 99%

Lack of K1b9 light chains in Basilea rabbits is probably due to a mutation in an acceptor site for mRNA splicing.

Lamoyi¹,

Mage²

1985

The Journal of Experimental Medicine

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Four forms of r immunoglobulin chains, known as the b4, b5, b6, and b9 allotypes, are products of allelic genes at the r 1 locus in domestic rabbit populations (1). A gene (K2) for a second r chain isotype (K2) is apparently present in all rabbits (2-5); one allotypic form of this gene is expressed at low levels in wild rabbits and some rabbits of b9 allotype (6-10). The Basilea strain was developed by Kelus and Weiss (11) from such a b9 rabbit in which an apparent mutation resulted in failure to produce the major type of Ig K light chains (K1). In these rabbits, the majority of Ig bear ~, light chains, and a small proportion bear r chains of the second isotype (K2) (8,(11)(12)(13). To understand the unusual r chain expression in Basilea rabbits, we have undertaken an analysis of the r genes in these animals. This report describes our investigations of the molecular basis for the loss of expression of K1 chains in the Basilea mutant.Rabbits are unusual in that they have two constant region r chain (C,) 1 genes (4, 5, 14-16). Although they have not yet been physically linked (4), the ~1 and ~2 genes are transmitted as linked traits in breeding colonies, and thus far no recombinants have been observed (6, 7, 9-11). The rl and r2 genes each have their own J (joining region) clusters (3, 5, 15). However, it is not known whether both Ca genes associate with the same variable region K chain (V~) gene pool. CK 1 genes show extensive polymorphism. Although the allelic b allotypes were first defined by serological and chemical analyses, the polymorphisms have now been studied by DNA sequencing (reviewed in l, 16-18). The DNA sequence homologies of the portions encoding K1 constant regions (C,1) range from 79% (b5 to b9) to 86% (b4 to b5) (16, 17). The known C~2 sequences are most similar to C,1 b9 (~89% homology) (17, 18). We used probes from the previously characterized cDNA (5, 18) and genomic clones to show, by Southern hybridization and restriction mapping, that both ~ 1 and K2 genes are present in DNA of Basilea rabbits, and that there are no detectable gross insertions, deletions, or other rearrangements in the K1 gene. For a finer analysis, we isolated and sequenced the mutant rlb9 gene. We found a G ~ A change in the highly conserved AG dinucleotide of the 3' acceptor splice site of the J-C intron. This substitution at ~ Abbreviations used in this paper: C, constant region; IVS, intervening sequence; J, joining region; SSC, saline sodium citrate; SDS, sodium dodecyl sulfate; UT, untranslated region; V, variable region; Y, pyrimidine.

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Genetics and expression of kappa-type light chains in Basilea rabbits

et al. 1984

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In contrast to rabbits of b4, b5, b6, and b9 allotypes whose serum immunoglobulins (Igs) are predominantly composed of kappa-type light chains, rabbits of the mutant Basilea strain have serum Igs that are largely of lambda type. We prepared several antisera that recognized a minor K2 (bas) light chain that is produced by Basilea rabbits. With these antisera we identified the K2 (bas) isotype in the serum of the original b9/b9 male rabbit whose offspring displayed the Basilea mutant phenotype. It was present in one half of his nonmutant offspring which inherited b9 from him and another b allotype from their mothers. Breeding was conducted both in Basel and at the NIH to develop and maintain colonies of mutant Basilea strain rabbits. The data obtained during colony development confirm that the trait of expression of the bas allotype maps to the same genetic region (b locus) that is known to control the allelic b allotypes b4, b5, b6 and b9. Homozygotes or heterozygotes of b4, b5 or b6 allotype (bb/bb) were mated with homozygous bbas / bbas rabbits to produce F1s , and then F2s as well as progeny of backcrosses to both homozygous parental types (bb/bb and bbas / bbas ) were produced. The bas allotype segregates as an allele (or pseudoallele ) at the b locus although there was a deficiency in recovery of homozygous bas offspring in both the F2 and backcross matings to bbas / bbas parental type in the NIH colony. This selective deficiency may reflect a deleterious effect on survival of homozygous bas progeny.

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BASILEA KAPPA LIGHT CHAINS OF RABBIT IMMUNOGLOBULINS

Cited by 8 publications

References 13 publications

In Utero Suppression of K2 Isotype in Homozygous Bas/Bas Rabbits Through Embryo Transfer

In Utero Suppression of K2 Isotype in Homozygous Bas/Bas Rabbits Through Embryo Transfer

Lack of K1b9 light chains in Basilea rabbits is probably due to a mutation in an acceptor site for mRNA splicing.

Genetics and expression of kappa-type light chains in Basilea rabbits

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