A second rabbit kappa isotype.

Benammar, A; Cazenave, Pierre‐André

doi:10.1084/jem.156.2.585

Cited by 44 publications

(10 citation statements)

References 29 publications

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“…In general, the j chain locus consists of multiple V regions, a small cluster of J segments and a single C region. The only documented exception to this rule is the rabbit, which seems to have two Cj genes [9,10]. In contrast, the k locus usually consists of multiple V regions followed by several C region gene segments, where one or several J segments are positioned in front of each C region [11,12].…”

Section: Introductionmentioning

confidence: 99%

High variability in complementarity‐determining regions compensates for a low number of V gene families in the λ light chain locus of the platypus

Johansson¹,

Salazar²,

Aveskogh³

et al. 2005

Eur J Immunol

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Based on the analysis of a panel of variable (V) region sequences from the Australian duck-billed platypus and the Australian short beaked echidna, the monotremes were found to express a highly diversified Vk repertoire. High variability was observed both in sequence and in length of all three CDR regions. However, all monotreme sequences were found to form a separate branch on a distance tree, and the monotremes appear to express only two Vk gene families. The appearance of all Vk gene segments in one branch on the distance tree gives further support for the notion that deletions of entire V region clans or families, followed by successive rounds of gene duplications may be a relatively common phenomenon during vertebrate evolution. Four different constant region sequences were also identified and a preferential use of certain J segments to each constant region was observed. A more detailed picture of the locus was obtained by analysis of genomic DNA by Southern blot and PCR. The organization of the lambda locus involves multiple V and several constant region genes with one or several joining segments positioned upstream of each constant region, similar to the organization in mouse and man. An mRNA frequency analysis shows that the k light chain accounts for more than 90% of the light chain transcripts in the spleen. The abundance and the high variability indicate that light chain diversity at the k locus contributes significantly to the antigen-binding repertoire in monotremes. A high k to j light chain ratio also indicates that variability in the CDR regions is more important for the repertoire size than the total number of V gene families.

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Section: Introductionmentioning

confidence: 99%

High variability in complementarity‐determining regions compensates for a low number of V gene families in the λ light chain locus of the platypus

Johansson¹,

Salazar²,

Aveskogh³

et al. 2005

Eur J Immunol

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“…In contrast to the situation in humans and mice, in domestic rabbits two K chain loci, K) and K2, encode the K chain bearing the nominal b allotype of the rabbit and the bas chain expressed in wild rabbits and in rabbits of the Basilea strain, respectively (1,2).…”

mentioning

confidence: 99%

Evolution of the immunoglobulin kappa light chain locus in the rabbit: evidence for differential gene conversion events.

Akimenko¹,

Mariamé²,

Rougeon³

1986

Proc. Natl. Acad. Sci. U.S.A.

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The rabbit Kc light chain gene family is characterized by the presence of two constant region (CQ) genes; the Cd gene encodes the constant region of the principal rabbit immunoglobulin light chain, the CK2 gene being not or very poorly expressed in domestic rabbits. There exist four major KI alleles (b4, b5, b6, and b9), which are unequally expressed in heterozygous rabbits at the K) locus. Here, we compare the nucleotide sequences of the joining (J) clusters of the K light chain gene (JK) linked to the b4K2 locus and to the b and b9 alleles at the K) locus. As for CK genes, there is evidence for intergenic conversion between the Jud and JK,2 clusters as well as maximum divergence in the expressedJ segments. The b9Jd cluster differs from its b4 counterpart in that two out of the five JK segments (Ji and J2) are expressed instead of only one. This implies that preferential expression of the b4 allele as compared to the b9 allele is not only correlated to the number of available Je pieces. The b9 J2 segment is functional in spite of the presence of a termination codon immediately upstream of its coding region. Two major structural differences were observed between the J-C intron sequences of the b9 and b4 alleles; namely a 160-base-pair deletion of an A+T-rich sequence in b9 (which also occurs in the K2 locus) and a 10-base-pair deletion plus some substitutions in the region corresponding to the mouse K intron activating element. These differences could underlie the lower transcriptional rate of the b9 allele.The rabbit immunoglobulin K light chain gene family constitutes an interesting model for the study of complex allele evolution and of the cis elements that control gene expression. In contrast to the situation in humans and mice, in domestic rabbits two K chain loci, K) and K2, encode the K chain bearing the nominal b allotype of the rabbit and the bas chain expressed in wild rabbits and in rabbits of the Basilea strain, respectively (1, 2).In mature B cells of rabbits heterozygous for the K) locus, the two alleles are unequally expressed. The following "pecking order" is observed: b4 > bS > b6 > b9 with a b4/b9 allelic ratio of 80:20 (3-6). These alleles are characterized by a high level of divergence at the protein level (ranging from 22 to 33% of divergence). Structural analysis of the corresponding genes has suggested that most of the differences have been generated by gene conversion (7). Another remarkable feature of the K) locus is that, at least in the case of the b4 allele, only one out of the five joining (J) segments of the K light chain (QJ) is functional (8, 9). The decrease in diversity that could result from this limited combinatorial potential is compensated for by an increased junctional variation during the V-J (V, variable) recombination because of nucleotide deletions in the JK segments and length heterogeneity of the VK germ-line segments (10). From nucleotide sequencing data of the human, mouse, and rabbit genes, a highly conserved region has been identified within the J-CK intro...

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“…Recently, a Basilea strain of rabbit has been developed that expresses low amounts of bas K light chains and exhibits compensatory production of X light chains (4). Experiments from four laboratories indicate that bas is an isotypic form of rabbit K (K2) (5)(6)(7)(8)(9)(10). These and earlier observations of latent (unexpected) allotype expression have led to proposals that rabbit K allotypes are in fact isotypes whose expression is regulated in allelic fashion (11)(12)(13)(14).…”

mentioning

confidence: 99%

Kappa-chain allotypes and isotypes in the rabbit: cDNA sequences of clones encoding b9 suggest an evolutionary pathway and possible role of the interdomain disulfide bond in quantitative allotype expression.

McCartney-Francis¹,

Skurla²,

Mage³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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The constant regions of rabbit K light chains are unusual because the sequences of the allotypic forms can differ more from each other than do some variable regions with which they associate. We report the nucleic acid sequence of a full-length cDNA clone of b9 allotype and show comparisons to available sequences of the rabbit K allotypes b, b5, and bas-N4. Our analyses suggest that the primordial rabbit K gene encoded a bas-like sequence. They also reveal a surprising difference in the position of the variable region cysteine that forms the interdomain disulfide bond that is unique to most rabbit K chains. One b9 cDNA sequence lacks the usual cysteine-80 and instead encodes cysteine-108, which in three-dimensional models appears capable of forming the interdomain disulfide bond with cysteine-171 in the constant region. A partial sequence of a second b9 clone encodes both cysteine-80 and cysteine-108; the translation product of this clone could have a free reactive sulfitydryl group that might lead to an unstable nonfunctional Ig molecule. The fact that pre-B cells with b9 K chains do not differentiate and expand into productive Ig-producing cells with frequencies comparable to the other allotypes may be explained if a substantial proportion of the gene products have a free sulfhydryl group. Our sequence results suggest that in cells differentiating to produce K light chains of b9 allotype the number and location of the cysteines influence immunoglobulin expression.

show abstract

A second rabbit kappa isotype.

Cited by 44 publications

References 29 publications

High variability in complementarity‐determining regions compensates for a low number of V gene families in the λ light chain locus of the platypus

High variability in complementarity‐determining regions compensates for a low number of V gene families in the λ light chain locus of the platypus

Evolution of the immunoglobulin kappa light chain locus in the rabbit: evidence for differential gene conversion events.

Kappa-chain allotypes and isotypes in the rabbit: cDNA sequences of clones encoding b9 suggest an evolutionary pathway and possible role of the interdomain disulfide bond in quantitative allotype expression.

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