Selective usage of IGLV lambda (IgVλ) segments in CLL Igλ gene rearrangements

Original article


Abusedra A 1.; Bybee A 2 Laffan M 2 Samson B 2 Apperley JF 2

1-Department of Microbiology,Faculty of Medicine,Garyounis University, Benghazi Libya 2-Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN

Garyounis Medical Journal Vol. 22, No.1. 2005:8-21


Background and objectives: Although approximately 40% of antibodies found in human serum contain lg light chains, the human λ locus was until recently poorly characterised at the molecular level. We have analyzed rearranged Vλ genes in order to show lambda restriction (immunophenotyping) in 163 cases of lymphoproliferative disorders (117 Chronic lymphoplastic leukemia(CLL), 14 multiple myeloma(MM), 18 AL arnyloidosis, 8 hairy cell leukaemia (HCL) and 6 lymphoma).
Materials and Methods: Using Vλ and Jλ consensus primers, products were generated by PCR in 111 of these patients (68%). Sequence analysis confirmed these to be rearranged Igλ sequences.
Results and conclusion: Clonal λ gene rearrangements were detected in 90 patients with CLL (77%), 6/8 with HCL (75%) and 4/6 with lymphoma (67%) but in only 5 of the MM patients (36%) and 6 with primary AL amyloidosis (33%). Variable success rates could be attributed to characteristic differences in percenage of clonal cells and somatic mutation rates. 16 of the 31 known functional Vλ genes were used. Detailed sequence analysis in 5/6 HCL and 52/55 CLL cases showed little or no mutation from the germ-line. Comparison of Igλ gene usage in the 90 CLLs with the normal B cell repertoire suggests that there may be a significant preferential usage of 1GLV3S2 (IGLV3-21 *01) in CLL.

Keywords: immunoglobulin gene rearrangement, Lymphoproliferative disorders, somatic mutation