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Blood, 15 November 2005, Vol. 106, No. 10, pp. 3575-3583.
Prepublished online as a Blood First Edition Paper on August 2, 2005; DOI 10.1182/blood-2005-04-1511.
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Submitted April 14, 2005
Accepted July 13, 2005
Immunoglobulin light chain repertoire in chronic lymphocytic leukemia
Kostas Stamatopoulos*, Chrysoula Belessi, Anastasia Hadzidimitriou, Tatjana Smilevska, Evangelia Kalagiakou, Katerina Hatzi, Niki Stavroyianni, Anastasia Athanasiadou, Aliki Tsompanakou, Theodora Papadaki, Garyfallia Kokkini, George Paterakis, Riad Saloum, Nikolaos Laoutaris, Achilles Anagnostopoulos, and Athanasios Fassas
Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece
Hematology Department, Nikea General Hospital, Piraeus, Greece
Hemopathology Department, Evangelismos Hospital, Athens, Greece
Hematology Department, Sismanogleion Hospital, Athens, Greece
Immunology Department, G. Gennimatas Hospital, Athens, Greece
* Corresponding author; email: stavstam{at}otenet.gr.
Immunoglobulin kappa (IGK) and lambda (IGL) light chain repertoire was analyzed in 276 CLL cases and compared to 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); 90/179 IGK sequences (50.3%) 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); 44/97 IGL sequences (45.4%) were mutated. Subsets with "CLL-biased", homologous CDR3 regions were identified: (i) IGKV2-30-IGKJ2, 7 sequences with homologous KCDR3, 5/7 associated with homologous IGHV4-34 heavy chains; (ii) IGKV1-39/1D-39-IGKJ1/4, 4 unmutated sequences with homologous KCDR3, 2/4 associated with homologous IGHV4-39 heavy chains; (iii) IGKV1-5-IGKJ1/3, 4 sequences with homologous KCDR3, 2/4 associated with unmutated non-homologous IGHV4-39 heavy chains; (iv) IGLV1-44-IGLJ2/3, 2 sequences with homologous LCDR3, associated with homologous IGHV4-b heavy chains; (v) IGLV3-21-IGLJ2/3, 9 sequences with homologous LCDR3, 3/9 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 which display homologous CDR3 regions provides further evidence for the role of antigen in CLL pathogenesis.
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