Ordered recombination of immunoglobulin light chain genes occurs at the IGK locus but seems less strict at theIGL locus

Blood ◽  
2001 ◽  
Vol 97 (4) ◽  
pp. 1001-1008 ◽  
Author(s):  
Mirjam van der Burg ◽  
Talip Tümkaya ◽  
Marjan Boerma ◽  
Sandra de Bruin-Versteeg ◽  
Anton W. Langerak ◽  
...  
Keyword(s):  
Light Chain ◽  
Messenger Rna ◽  
Somatic Mutations ◽  
Cell Model ◽  
Complete Analysis ◽  
Immunoglobulin Light Chain ◽  
Main Determinant ◽  
Heavy Chains ◽  
Single Cell Model ◽  
Rearrangement Processes

Abstract Regulation of allelic and isotypic exclusion of human immunoglobulin (Ig) light-chain genes was studied in 113 chronic B-cell leukemias as a “single-cell” model that allowed complete analysis of each light chain allele. Our data show that monospecific Ig light chain expression is in about 90% of cases determined by ordered recombination: Igκ gene (IGK) rearrangements, followed byIGK deletions and Igλ gene (IGL) rearrangements, resulting in the presence of only one functional Ig light chain rearrangement. In about 10% (10 cases), 2 functional Ig light chain rearrangements (IGK/IGL or IGL/IGL, but not IGK/IGK) were identified. This might be explained by the fact that regulation of the ordered recombination process is not fully strict, particularly when the IGL locus is involved. Unfavorable somatic mutations followed by receptor editing might have contributed to this finding. Eight of these 10 cases indeed contained somatic mutations. In cases with 2 functional Ig light chain rearrangements, both alleles were transcribed, but monospecific Ig expression was still maintained. This suggests that in these cases allelelic exclusion is not regulated at the messenger RNA level but either at the level of translation or protein stability or via preferential pairing of Ig light and Ig heavy chains. Nevertheless, ordered rearrangement processes are the main determinant for monospecific Ig light chain expression.

Sequence analysis of immunoglobulin light chain messenger RNA

Nature ◽  
1974 ◽  
Vol 252 (5482) ◽  
pp. 354-359 ◽  
Author(s):  
C. Milstein ◽  
G. G. Brownlee ◽  
E. M. Cartwright ◽  
J. M. Jarvis ◽  
N. J. Proudfoot
Keyword(s):  
Sequence Analysis ◽  
Light Chain ◽  
Messenger Rna ◽  
Immunoglobulin Light Chain

Immunoglobulin Light Chain Repertoire in Chronic Lymphocytic Leukemia (CLL): Recognition of Subsets with “CLL-Specific” CDR3 Regions and Associations with Heavy Chains.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 769-769 ◽  
Author(s):  
Kostas Stamatopoulos ◽  
Chrysoula Belessi ◽  
Anastasia Hadzidimitriou ◽  
Evangelia Kalagiakou ◽  
Tatjana Smilevska ◽  
...  
Keyword(s):  
Light Chain ◽  
Lymphocytic Leukemia ◽  
Molecular Processes ◽  
Immunoglobulin Light Chain ◽  
Heavy Chains ◽  
Molecular Features ◽  
Gene Usage ◽  
Region Length ◽  
Unequal Length

Abstract We analyzed immunoglobulin light chain (IgLC) repertoire in a series of 253 typical, unselected CLL cases and compared CLL IgLC sequences to GenBank IgLC sequences from normal, autoreactive and neoplastic cells. The present series included 165 κ- and 88 λ-CLL cases. Twenty-three functional IGKV genes were used in IGKV-J rearrangements in κ-CLL; the most frequent genes were: 3-20/A27 (25 cases), 1-39-1D-39/O2-O12 (19 cases), 4-1/B3 (16 cases), 1-5/L12 (15 cases), 2-30/A17 (13 cases) and 1-8/L9 (10 cases). There were 55/165 unmutated sequences (33%), 44/165 sequences (27%) with 97-99,6% homology to germline and 66/165 sequences (40%) with less than 97% homology. KCDR3 region length ranged from 6–11 (median, 9) aminoacids (aa). N nucleotides (median 3, range 1–12) were detected in 85/165 rearrangements (51.5%). IGKJ3-5 gene usage was observed in 51/165 rearrangements (30%); interestingly, IGKJ3-5 genes were used in 7/8 IGKV3-11 and 4/5 IGKV1-9 rearrangements. Subsets with homologous and “CLL-specific” KCDR3 regions were identified: IGKV2-30, 5 mutated sequences with identical KCDR3 (MQGTYWPYT), 3/5 associated with IGHV4-34 utilizing heavy chains with a similar HCDR3 of 20 aa; IGKV1-39/1D-39, 3 unmutated sequences with identical KCDR3 (QQSYSTTPLT), all associated with IGHV4-39 utilizing heavy chains with a similar HCDR3 of 19 aa; IGKV1-5, 4 unmutated sequences with identical KCDR3 (QQYNSYPWT), 2/4 associated with unmutated IGHV4-39 utilizing heavy chains with a HCDR3 of unequal length. Twenty-six functional IGLV genes were used in IGLV-J rearrangements in λ-CLL; the most frequent genes were: IGLV2-8/1-2 (14 cases), 3-21/2-14 (13 cases), 2-14/1-4 and 1-44/1-16 (7 cases each). There were 24/88 unmutated sequences (27%), 33/88 sequences (37,5%) with 97-99,6% homology to germline and 31/88 sequences (35%) with less than 97% homology. LCDR3 region length ranged from 8-13 aa (median, 11). N nucleotides (median 3, range 1-15) were detected in 42/88 rearrangements (47.7%). The IGLJ1 gene was used in 18/88 rearrangements (20%); all other rearrangements used the IGLJ3*01/*02 genes. Subsets with homologous and “CLL-specific” LCDR3 regions were identified: IGLV1-44, 2 sequences with very similar LCDR3 (AAWDDSLNGP/QV), both associated with IGHV4-b utilizing heavy chains with a similar HCDR3 of 11 aa; IGLV3-21, 7 sequences all with identical LCDR3 (QVWDSGSDHPWV), 3/7 associated with IGHV3-21 utilizing heavy chains with a similar HCDR3 of 9 aa. These results document that IgLC repertoire in CLL is biased by both intrinsic molecular processes as well as selection after LC expression. Genes that have been reported to be overexpressed in the normal and autoimmune disorders were also found to be overrepresented in the CLL repertoire, often with “CLL-specific” molecular features. Finally, the existence of subgroups with homologous CDR3 regions associated with similar heavy chains provides further evidence for the role of antigen selection in CLL pathogenesis.

One siRNA pool targeting the λ constant region stops λ light-chain production and causes terminal endoplasmic reticulum stress

Blood ◽  
2014 ◽  
Vol 123 (22) ◽  
pp. 3440-3451 ◽  
Author(s):  
Ping Zhou ◽  
Xun Ma ◽  
Lakshmanan Iyer ◽  
Chakra Chaulagain ◽  
Raymond L. Comenzo
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Light Chain ◽  
Antibody Production ◽  
Plasma Cells ◽  
Light Chains ◽  
Constant Region ◽  
Immunoglobulin Light Chain ◽  
Heavy Chains ◽  
Key Points

Key PointsImmunoglobulin light-chain and antibody production by plasma cells is significantly reduced by siRNA for the light-chain constant region. In plasma cells making intact antibodies, knockdown of light chains can cause terminal ER stress because of unpaired heavy chains.

scholarly journals Immunocytochemical identification and localization of immunoglobulin A within Paneth cells of the rat small intestine.

1976 ◽  
Vol 24 (10) ◽  
pp. 1085-1092 ◽  
Author(s):  
S L Erlandsen ◽  
C B Rodning ◽  
C Montero ◽  
J A Parsons ◽  
E A Lewis ◽  
...  
Keyword(s):  
Light Chain ◽  
Cell Function ◽  
Paneth Cell ◽  
Immunoglobulin A ◽  
Cross Reactivity ◽  
Paneth Cells ◽  
Immunoglobulin Light Chain ◽  
Specific Staining ◽  
Heavy Chains ◽  
Purified Antigen

Light microscopic immunocytochemistry was used to identify Paneth cells by their lysozyme content and to detect immunoglobulin antigens within a subpopulation of these cells. Antisera specific for the heavy chains of rat or human immunoglobulin A and for immunoglobulin light chain antigens produced specific staining of rat Paneth cells. The distribution of immunoglobulin staining varied between adjacent Paneth cells in the same crypt and between Paneth cells in adjacent crypts, as well as between Paneth cell populations of different animals. No staining of rat Paneth cells was detected using antisera specific for the heavy chain of immunoglobulins G or M. The specific staining of Paneth cells for immunoglobulin A and light chain antigens was blocked by absorption of each antiserum with its respective purified antigen. Absorption of these antisera with purified rat lysozyme did not affect staining and thereby eliminated the possibility of immunologic cross-reactivity between lysozyme and immunoglobulin antigens. It is suggested, in light of current concepts of Paneth cell function, that the immunoglobulin staining of Paneth cells may reflect their ability to phagocytize immunoglobulin A-coated microorganisms or immune complexes containing immunoglobulin A.

Immunoglobulin light chain repertoire in chronic lymphocytic leukemia

Blood ◽  
2005 ◽  
Vol 106 (10) ◽  
pp. 3575-3583 ◽  
Author(s):  
Kostas Stamatopoulos ◽  
Chrysoula Belessi ◽  
Anastasia Hadzidimitriou ◽  
Tatjana Smilevska ◽  
Evangelia Kalagiakou ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Light Chain ◽  
Lymphocytic Leukemia ◽  
Immunoglobulin Light Chain ◽  
Neoplastic Cells ◽  
Heavy Chains ◽  
Immunoglobulin Kappa ◽  
Complementarity Determining Region ◽  
Immunoglobulin Lambda

AbstractImmunoglobulin kappa (IGK) and immunoglobulin lambda (IGL) light chain repertoire was analyzed in 276 chronic lymphocytic leukemia (CLL) cases and compared with the relevant repertoires from normal, autoreactive, and neoplastic cells. Twenty-one functional IGKV genes were used in IGKV-J rearrangements of 179 kappa-CLL cases; the most frequent genes were IGKV3-20(A27), IGKV1-39/1D-39(O2/O12), IGKV1-5(L12), IGKV4-1(B3), and IGKV2-30(A17); 90 (50.3%) of 179 IGK sequences were mutated (similarity < 98%). Twenty functional IGLV genes were used in IGLV-J rearrangements of 97 lambda-CLL cases; the most frequent genes were IGLV3-21(VL2-14), IGLV2-8(VL1-2), and IGLV2-14(VL1-4); 44 of 97 IGL sequences (45.4%) were mutated. Subsets with “CLL-biased” homologous complementarity-determining region 3 (CDR3) were identified: (1) IGKV2-30-IGKJ2, 7 sequences with homologous kappa CDR3 (KCDR3), 5 of 7 associated with homologous IGHV4-34 heavy chains; (2) IGKV1-39/1D-39-IGKJ1/4, 4 unmutated sequences with homologous KCDR3, 2 of 4 associated with homologous IGHV4-39 heavy chains; (3) IGKV1-5-IGKJ1/3, 4 sequences with homologous KCDR3, 2 of 4 associated with unmutated nonhomologous IGHV4-39 heavy chains; (4) IGLV1-44-IGLJ2/3, 2 sequences with homologous lambda CDR3 (LCDR3), associated with homologous IGHV4-b heavy chains; and (5) IGLV3-21-IGLJ2/3, 9 sequences with homologous LCDR3, 3 of 9 associated with homologous IGHV3-21 heavy chains. The existence of subsets that comprise given IGKV-J/IGLV-J domains associated with IGHV-D-J domains that display homologous CDR3 provides further evidence for the role of antigen in CLL pathogenesis.

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