Probing the role of λ6 immunoglobulin light chain dimerization in amyloid formation

2016 ◽  
Vol 1864 (4) ◽  
pp. 409-418 ◽  
Author(s):  
Mathieu Laporte Wolwertz ◽  
Phuong Trang Nguyen ◽  
Noé Quittot ◽  
Steve Bourgault
Keyword(s):  
Light Chain ◽  
Amyloid Formation ◽  
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.

The Role of CD40–CD40 Ligand (CD154) Interactions in Immunoglobulin Light Chain Repertoire Generation and Somatic Mutation

2001 ◽  
Vol 100 (1) ◽  
pp. 71-81 ◽  
Author(s):  
Nancy L. Monson ◽  
Sandra J. Foster ◽  
Hans-Peter Brezinschek ◽  
Ruth I. Brezinschek ◽  
Thomas Dörner ◽  
...  
Keyword(s):  
Somatic Mutation ◽  
Light Chain ◽  
Cd40 Ligand ◽  
Immunoglobulin Light Chain

scholarly journals Heat-induced native dimerization prevents amyloid formation by variable domain from immunoglobulin light-chain REI

FEBS Journal ◽  
2017 ◽  
Vol 284 (18) ◽  
pp. 3114-3127 ◽  
Author(s):  
Marina Nawata ◽  
Hirotaka Tsutsumi ◽  
Yuta Kobayashi ◽  
Satoru Unzai ◽  
Shouhei Mine ◽  
...  
Keyword(s):  
Light Chain ◽  
Variable Domain ◽  
Amyloid Formation ◽  
Immunoglobulin Light Chain

scholarly journals Role of Glycosaminoglycan Sulfation in the Formation of Immunoglobulin Light Chain Amyloid Oligomers and Fibrils

2010 ◽  
Vol 285 (48) ◽  
pp. 37672-37682 ◽  
Author(s):  
Ruiyi Ren ◽  
Zhenning Hong ◽  
Haiyan Gong ◽  
Kate Laporte ◽  
Martha Skinner ◽  
...  
Keyword(s):  
Light Chain ◽  
Immunoglobulin Light Chain ◽  
Amyloid Oligomers

scholarly journals The Critical Role of the Constant Region in Thermal Stability and Aggregation of Amyloidogenic Immunoglobulin Light Chain

Biochemistry ◽  
2010 ◽  
Vol 49 (45) ◽  
pp. 9848-9857 ◽  
Author(s):  
Elena S. Klimtchuk ◽  
Olga Gursky ◽  
Rupesh S. Patel ◽  
Kathryn L. Laporte ◽  
Lawreen H. Connors ◽  
...  
Keyword(s):  
Thermal Stability ◽  
Light Chain ◽  
Critical Role ◽  
Constant Region ◽  
Immunoglobulin Light Chain

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.

scholarly journals The effects of sodium sulfate, glycosaminoglycans, and Congo red on the structure, stability, and amyloid formation of an immunoglobulin light-chain protein

2006 ◽  
Vol 15 (7) ◽  
pp. 1710-1722 ◽  
Author(s):  
Richard W. Mclaughlin ◽  
Janelle K. De Stigter ◽  
Laura A. Sikkink ◽  
Elizabeth M. Baden ◽  
Marina Ramirez-Alvarado
Keyword(s):  
Light Chain ◽  
Congo Red ◽  
Sodium Sulfate ◽  
Structure Stability ◽  
Amyloid Formation ◽  
Immunoglobulin Light Chain
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