Human immunoglobulin C lambda 6 gene encodes the Kern+Oz-lambda chain and C lambda 4 and C lambda 5 are pseudogenes.

Abstract

Six nonallelic immunoglobulin A constant region genes have been previously characterized on a 40-kilobase stretch of DNA. The nucleotide sequences of the three upstream genes of this cluster (Cj1, Cx2, Ck3) have been determined by other workers and shown to encode, respectively, the isotypic Mcg, Kern-Oz-, and Kern-Oz+ constant region of the A chains. In this paper, we report the sequence of the three downstream genes of this cluster and show that two of them (CA4 and Cx5) are pseudogenes. However, Ck6 encodes a Kern+Oz-chain and corresponds to the fourth isotype described among the A proteins sequenced so far. A potentially active J4 (oining) segment, with the canonical heptamer and nonamer sequences for rearrangement, is located 1.5 kilobases upstream of Cx6. The amino acid sequence encoded by the Cx6 gene is compared with the constant region sequences of various monoclonal Bence Jones A proteins. Allotypic and isotypic differences confirm the polymorphism and complexity of the human Ck locus.In humans, the constant (C) region of the immunoglobulin X light chains consists of at least four nonallelic or isotypic forms that differ by limited amino acid substitutions to produce the serological markers Kern (Ke) (1, 2), Oz (3-5), and Mcg (6, 7). Several additional substitutions have been described (8-16), but it is unknown whether these represent allelic variants or distinct isotypes. The human immunoglobulin X light chain genes have been mapped to chromosome 22 (17) at band q1l (18,19), and six nonallelic X C region genes (CxJ to Cx6) have been characterized on a 40-kilobase (kb) stretch of DNA (20). The number of CA genes varies between six and nine per haploid genome (21). These variations were detected by restriction fragment length polymorphism (21) and seem to have arisen from unequal meiotic crossing-over with a duplication of the CA2 and CA3 genes. Moreover, three additional CA-like genes have been recently identified, which map on different stretches of DNA and are nonallelic (22). One of these is a pseudogene, whereas the two others encode a putative A chain C region whose sequence differs from that of the X chains described so far.Only three QC genes (CA1, Cx2, and CA3) belonging to the cluster described by Hieter have been sequenced (20), and they have been shown to encode, respectively, the Mcg, Ke-Oz-, and Ke-Oz+ C region of the A chains. In this paper, we report the sequences* of the three genes located downstream in this cluster and show that two of them (CA4 and CA5) are pseudogenes, whereas CA6 encodes a Ke+Oz-chain, the fourth isotype described among the proteins sequenced so far. This CK6 gene has a potentially active JX6 joining region, with the canonical heptamer and nonamer sequences for rearrangement, 1.5 kb upstream of the coding C region. MATERIALS AND METHODSConstruction of a Phage Library from LY67 DNA. DNA prepared from LY67 cells (a X-producing Burkitt's lymphoma) (23)

Sequence analyses of three immunoglobulin G anti-virus antibodies reveal their utilization of autoantibody-related immunoglobulin Vh genes, but not V lambda genes.

“…1); its Jh region deviated from a Jh5 sequence by one silent change ( 11 ), while its Cy 1 region was identical to the reported Cy 1 sequence over a 77-bp region (37). On the other hand, the la3h3 L chain utilized a JX3 and CX3 gene (38,39), instead ofthe closely related CX2 gene, based on a single diagnostic base (A vs. G) at nucleotide position 363 (Fig. 4) …”

Preferential utilization of a novel vλ3 gene in monoclonal rheumatoid factors derived from the synovial cells of rheumatoid arthritis patients

“…in the first complementarity-determining region (CDR1). In addition, lalb42 used a JA2/3 gene, since both Jh genes were identical in their coding regions (Table 1 and Figure 1) (17,18). One nucleotide in the CDR3 of lalb42 cannot be accounted for by either the Vhl or the Jh2/3 genes, which suggests the existence of either an N region (19) or a longer VA gene segment ( Figure 1).…”

“…Humla3c93 used a Jh2/3 gene, beginning at position 292 (Table 1 and Figure 2B) (17,18). Assuming the VA gene-encoded region ends at position 288, the …”

“…Humla3d53 was identical to Humla3c93 and the lv3c93 germline gene (Figure 3). The remainder of la3d53 used a JAl gene (Table 1 and Figure 2B) (17,18).…”

Immunoglobulin lambda isotype gene rearrangements in B cell malignancies

“…6 Cluster A is located proximal to the J-C regions and contains families V II and III, cluster B contains family V I, one member of family IV, and families V, VII, and IX, whereas the remaining members of family V IV, as well as families VI, VIII and X are grouped in cluster C. 6 The gene regions J-C 1, J-C 2, J-C 3, and J-C 7 are functional, while J-C 4, J-C 5, and J-C 6 are non-functional (pseudo) gene regions. 2,7,8 The J-C 4 region has a deletion of approximately 1150 bp and in the 3′ end of the C 5 exon 11 bp are deleted. 2 Moreover, the recombination signal sequences (RSS) of the J 4 and J 5 gene segments do not con-tain all essential nucleotides.…”