Stamatopoulos Kostas, Belessi Chrysoula, Hadzidimitriou Anastasia, Smilevska Tatjana, Kalagiakou Evangelia, Hatzi Katerina, Stavroyianni Niki, Athanasiadou Anastasia, Tsompanakou Aliki, Papadaki Theodora, Kokkini Garyfallia, Paterakis George, Saloum Riad, Laoutaris Nikolaos, Anagnostopoulos Achilles, Fassas Athanasios
Hematology Department and Hematopoietic Cell Transplantation (HCT) Unit, G. Papanicolaou Hospital, Thessaloniki, Greece.
Blood. 2005 Nov 15;106(10):3575-83. doi: 10.1182/blood-2005-04-1511. Epub 2005 Aug 2.
Immunoglobulin 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.
对276例慢性淋巴细胞白血病（CLL）病例的免疫球蛋白κ（IGK）和免疫球蛋白λ（IGL）轻链库进行了分析，并与来自正常细胞、自身反应性细胞和肿瘤细胞的相关轻链库进行了比较。179例κ型CLL病例的IGKV-J重排中使用了21个功能性IGKV基因；最常见的基因是IGKV3-20（A27）、IGKV1-39/1D-39（O2/O12）、IGKV1-5（L12）、IGKV4-1（B3）和IGKV2-30（A17）；179个IGK序列中有90个（50.3%）发生了突变（相似性<98%）。97例λ型CLL病例的IGLV-J重排中使用了20个功能性IGLV基因；最常见的基因是IGLV3-21（VL2-14）、IGLV2-8（VL1-2）和IGLV2-14（VL1-4）；97个IGL序列中有44个（45.4%）发生了突变。鉴定出具有“CLL偏向性”同源互补决定区3（CDR3）的亚群：（1）IGKV2-30-IGKJ2，7个具有同源κ CDR3（KCDR3）的序列，7个中有5个与同源IGHV4-34重链相关；（2）IGKV1-39/1D-39-IGKJ1/4，4个未突变的具有同源KCDR3的序列，4个中有2个与同源IGHV4-39重链相关；（3）IGKV1-5-IGKJ1/3，4个具有同源KCDR3的序列，4个中有2个与未突变的非同源IGHV4-39重链相关；（4）IGLV1-44-IGLJ2/3，2个具有同源λ CDR3（LCDR3）的序列，与同源IGHV4-b重链相关；以及（5）IGLV3-21-IGLJ2/3，9个具有同源LCDR3的序列，9个中有3个与同源IGHV3-21重链相关。包含与显示同源CDR3的IGHV-D-J结构域相关的特定IGKV-J/IGLV-J结构域的亚群的存在，为抗原在CLL发病机制中的作用提供了进一步的证据。
