IMGT Repertoire (IG and TR)

Locus description: Human (Homo sapiens) IGL

DNA

Overview

The human IGL locus is located on the chromosome 22 [1], on the long arm, at band 22q11.2 [2]. IGL orphons have been identified on chromosomes 8 and 22. The total number of human IGL genes per haploid genome is 87-96 (93-102, if the orphons are included) of which 37-43 genes are functional.

The list of human IGL genes is available at IMGT/GENE-DB.

Human IGL locus at 22q11.2

The human IGL locus at 22q11.2 spans 1050 kilobases (kb). The orientation of the locus has been determined by the analysis of translocations, involving the IGL locus, in leukemia and lymphoma. Sequencing of the long arm of chromosome 22 showed that it encompasses about 35 megabases of DNA and that the IGL locus is localized at 6 megabases from the centromere [3]. Although the correlation between DNA sequences and chromosomal bands has not yet been made, the localization of the IGL locus can be refined to 22q11.2. The most 5' IGLV genes occupy the more centromeric position, whereas the IGLC genes, in 3' of the locus, are the most telomeric genes in IGL locus.
The human IGL locus consists of 73 to 74 IGLV genes [4,5-9], localized on 900 kb, 7 to 11 IGLJ and 7 to 11 IGLC genes depending on the haplotypes, each IGLC gene being preceded by one IGLJ segment [10-13]. Fifty-six to 57 IGLV genes belong to 11 subgroups, whereas 14 pseudogenes which are too divergent to be assigned to subgroups, have been assigned to 3 clans.
The potential genomic IGL repertoire comprises 29 to 33 functional IGLV genes belonging to 10 subgroups, 4-5 IGLJ, and 4-5 IGLC functional genes in the 7-IGLC gene haplotype. One, 2, 3 or 4 additional IGLC genes, each one probably preceded by one IGLJ, have been shown to characterize IGLC haplotypes with 8, 9, 10 or 11 genes [11,14-16], but these genes have not yet been sequenced [17].

Orphons

Six IGL genes have been found outside the main locus in other chromosomal localizations corresponding to 3 chromosomal orphon sets. These genes, designated as orphons, cannot contribute to the synthesis of the immunoglobulin lambda chains, even if they have an open reading frame (ORF). Two IGLV orphons have been identified on chromosome 8 at 8q11.2 and one of them belonging to subgroup 8 has been sequenced [18]. The recent sequencing of the chromosome 22q showed that the IGL locus is localized at 6 megabases from the centromere. Two IGLC orphons and two IGLV orphons have also been characterized on 22q outside of the major IGL locus [3].

Total number of human IGL genes

The total number of human IGL genes per haploid genome is 87-96 (93-102, if the orphons are included) of which 37-43 genes are functional [19].

IG and TR number of genes: Human
Nomenclature and overview of the human immunoglobulin genes (IMGT Education)

Nomenclature

IGLV gene nomenclature

Human IGLV genes are designated by a number for the subgroup, followed by a hyphen and a number for the localization from 3' to 5' in the locus [20,21].
Pseudogenes which could not be assigned to subgroups with functional genes are designated by a roman number between parentheses, corresponding to the clans followed by a hyphen and a number for the localization from 3' to 5' in the locus.
Clans comprise, respectively:
- clan I: IGLV1, IGLV2, IGLV6 and IGLV10 subgroup genes, and pseudogenes IGLV(I)-20, -38, -42, -56, -63, -68 and -70.
- clan II: IGLV3 subgroup genes.
- clan III: IGLV7 and IGLV8 subgroup genes.
- clan IV: IGLV5 and IGLV11 subgroup genes, and pseudogenes IGLV(IV)-53, -59, -64, -65 and 66-1.
  IGLV(IV)-66-1 has been identified in D87004 by IMGT curators (G. Folch, V. Giudicelli and M.-P. Lefranc).
- clan V: IGLV4 and IGLV9 subgroup genes, and pseudogenes IGLV(V)-58 and -66.
- clan VI: pseudogenes IGLV(VI)-22-1 and -25-1. IGLV(VI)-25-1 has been identified in D86994 by IMGT curators (N. Bosc and M.-P. Lefranc).
- clan VII: pseudogene IGLV(VII)-41-1.
Allelic polymorphisms by insertion/deletion concern the IGLV5-39 gene.
One, two, three or four additional IGLC genes, each one probably preceded by one IGLJ, have been shown to characterize IGLC haplotypes with 8, 9, 10 or 11 genes [11,14,15], but these genes have not yet been sequenced.

IMGT and HUGO gene nomenclatures

IMGT gene names have been approved by the Human Genome Organization (HUGO) Nomenclature Committee in 1999. Note that, in the HUGO symbols, parentheses of the pseudogene names are omitted. Otherwise all the gene names (symbols) are identical in IMGT and HUGO nomenclatures.
IGL definitions (full names) are identical (including parentheses) in IMGT and HUGO nomenclatures.

Links between IMGT and Entrez Gene

Click here for a complete list of the human immunoglobulin and T cell receptor IMGT gene names (symbols). This list provides the IMGT definition (full name), the gene functionality, the IMGT accession number of the reference sequence, the number of alleles per gene, and the GDB and Entrez Gene accession ID. The table below reports entries which concern the IGL locus or groups and are found in the OMIM, and Entrez Gene genome databases, and in HUGO:

IMGT name	IMGT definition (a)	OMIM	Entrez Gene	HUGO
IGL locus	Immunoglobulin lambda locus	-	3535	IGL@
IGLC group	Immunoglobulin lambda constant group	147220	3536	IGLC@
IGLJ group	Immunoglobulin lambda joining group	147230	8217	IGLJ@

(a) The locus definition is identical in IMGT, Entrez Gene and HUGO. The IMGT 'group' concept comprises genes of the major locus and of the chromosomal orphon sets, whereas the HUGO IG group symbols only refer to genes of the major locus.

Protein

Proteins encoded by the IGL locus are the immunoglobulin lambda chains. They result from the recombination (or rearrangement), at the DNA level, of two genes: IGLV and IGLJ, with deletion of the intermediary DNA to create a rearranged IGLV-J gene. The rearranged IGLV-J gene is transcribed with one of the IGLC genes and traslated into an immunoglobulin lambda chain. Translation of the variable germline genes involved in the IGLV-J rearrangements are available at Protein displays. Compared to the germline genes, the rearranged variable genes will acquire somatic mutations during the B cell differentiation in the lymph nodes, which will considerably increase their diversity. These somatic mutations can be analysed using the IMGT/V-QUEST tool. The junctions can be analysed with IMGT/JunctionAnalysis.

Alleles and mutations

Mutations which correspond to allelic polymorphisms of the functional germline IGLV, IGLJ and IGLC genes are described in Alignments of alleles [19] and Tables of alleles.

TRANSLOCATIONS

Translocations in which the human IGL locus is implicated frequently result from errors of the recombinase enzyme complexe (RAG1, RAG2, ...), responsable of the Immunoglobulin and T cell receptor V-J and V-D-J rearrangements, or from errors of the switch enzyme. IGLV or IGLJ recombination signals or isolated heptamer are observed at the breakpoints.

t(8;22)(q24;q11)
t(3;22)(q27;q11)

References:
[1]	Erikson, J., Martinis, J., Croce, J.M. "Assignment of the genes for human lambda immunoglobulin chains to chromosome 22" Nature, 294, 173-175 (1981) PMID:6795508
[2]	Emanuel, B.S., Cannizzaro, L.A., Magrath, I., Tsujimoto, Y., Nowell, P.C., Croce, C.M. "Chromosomal orientation of the lambda light chain locus: V lambda proximal to C lambda in 22q11" Nucl. Acids Res., 13, 381-387 (1985) PMID:3923432
[3]	Dunham, I., Shimizu, N., Roe, B.A., Chissoe, S., Hunt, A.R., Collins, J.E., Bruskiewich, R., Beare, D.M., Clamp, M., Smink, L.J., Ainscough, R., Almeida, J.P., Babbage, A., Bagguley, C., Bailey, J., Barlow, K., Bates, K.N., Beasley, O., Bird, C.P., Blakey, S., Bridgeman, A.M., Buck, D., Burgess, J., Burrill, W.D., O'Brien, K.P., et al. "The DNA sequence of human chromosome 22" Nature, 402, 489-495 (1999) PMID:10591208
[4]	Pallarès, N., Frippiat, J.-P., Giudicelli, V., Lefranc, M.-P. "IMGT Locus on Focus: The human immunoglobulin lambda variable (IGLV) genes and joining (IGLJ) segments" Exp. Clin. Immunogenet., 15, 8-18 (1998) PMID:9619396
[5]	Scaviner, D., Barbié, V., Ruiz, M., Lefranc, M.-P. "IMGT Locus on Focus: Protein display of the human immunoglobulin heavy, kappa and lambda variable and joining regions" Exp. Clin. Immunogenet., 16, 234-240 (1999) PMID:10575277
[6]	Frippiat, J.-P., Williams, S.C., Tomlinson, I.M., Cook, G.P., Cherif, D., Le Paslier, D., Collins J.E., Dunham, I., Winter, G., Lefranc, M.-P. "Organization of the human immunoglobulin lambda light-chain locus on chromosome 22q11.2" Hum. Mol. Genet., 4, 983-991 (1995) PMID:7655473
[7]	Kawasaki, K., Minoshima, S., Schooler, K., Kudoh, J., Asakawa, S., de Jong, P.J., Shimizu, N. "The organization of the human immunoglobulin lambda gene locus" Genome Research, 5, 125-135 (1995) PMID:9132267
[8]	Williams, S.C., Frippiat, J.-P., Tomlinson, I.M., Ignatovich, O., Lefranc, M.-P., Winter, G. "Sequence and evolution of the human germline V lambda repertoire" J. Mol. Biol., 264, 220-232 (1996) PMID:8951372
[9]	Kawasaki, K., Minoshima, S., Nakato, E., Shibuya, K., Shintani, A., Schmeits, J.L., Wang, J., Shimizu, N. "One-megabase sequence analysis of the human immunoglobulin lambda gene locus" Genome Research, 7, 250-261 (1997) PMID:9074928
[10]	Hieter, P.A., Hollis, G.F., Korsmeyer, S.J., Waldmann, T.A., Leder, P. "Clustered arrangement of immunoglobulin lambda constant region genes in man" Nature, 294, 536-540 (1981) PMID:6273747
[11]	Taub, R.A., Hollis, G.F., Hieter, P.A., Korsmeyer, S., Waldmann, T.A., Leder, P. "Variable amplification of immunoglobulin lambda light-chain genes in human populations" Nature, 304, 172-174 (1983) PMID:6306474
[12]	Dariavach, P., Lefranc, G., Lefranc, M.-P. "Human immunoglobulin C lambda 6 gene encodes the Kern+Oz lambda chain and C lambda 4 and C lambda 5 are pseudogenes" Proc. Nat. Acad. Sc. USA, 84, 9074-9078 (1987) PMID:3122211
[13]	Vasicek, T.J., Leder, P. "Structure and expression of the human immunoglobulin lambda genes" J. Exp. Med., 172, 609-620 (1990) PMID:2115572
[14]	Ghanem, N., Dariavach, P., Bensmana, M., Chibani, J., Lefranc, G., Lefranc, M.-P. "Polymorphism of immunoglobulin lambda constant region genes in populations from France, Lebanon and Tunisia" Exp. Clin. Immunogenet., 5, 186-195 (1988) PMID:2908491
[15]	Kay, P.H., Moriuchi, J., Ma, P.J., Saueracker, E. "An unusual allelic form of the immunoglobulin lambda constant region genes in the Japanese" Immunogenetics, 35, 341-343 (1992) PMID:1348496
[16]	Lefranc, M.-P., Pallarès, N., Frippiat, J.-P. "Allelic polymorphisms and RFLP in the human immunoglobulin lambda light chain locus" Hum. Genet., 104, 361-369 (1999) PMID:10394926
[17]	Lefranc, M.-P. "Locus maps and genomic repertoire of the human Ig genes" The Immunologist, 3, 80-87 (2000)
[18]	Frippiat, J.-P., Dard, P., Marsh, S., Winter, G., Lefranc, M.-P. "Immunoglobulin lambda light chain orphons on human chromosome 8q11.2" Eur. J. Immunol., 27, 1260-1265 (1997) PMID:9174619
[19]	Lefranc, M.-P., Lefranc, G. "The immunoglobulin Factsbook" Academic Press, Hartcourt Publishers Limited, London, UK, 458 pages (2001) ISBN:012441351X
[20]	Lefranc, M.-P. "Nomenclature of the human immunoglobulin genes" Current Protocols in Immunology, A.1P.1-A.1P.37 (2000)
[21]	Lefranc, M.-P. "IMGT Locus in Focus: Nomenclature of the human immunoglobulin lambda (IGL) genes" Exp. Clin. Immunogenet., 18, 242-254 (2001), PMID:11872955