Deng Lijuan, Song Yuqin, DingNing, Song Weiwei, Huang Huiying, Liu Weiping, Zhu Jun

Department of lymphoma, Peking University CancerHospital

Objective:While the epidemiologic associationbetween hepatitis B virus (HBV) infection and diffuse large B-cell lymphoma(DLBCL) is established, little is known more than this epidemiologic evidence. Method:We studied the immunoglobulin variable region in HBV surface antigen(HBsAg)-positive patients. Result: Total DNA was extracted fromformalin-fixed paraffin-embedded tissue sections from 47 of the 81HBsAg-positive DLBCL patients. Complete IGHV-D-J rearrangements and IGKV-Jrearrangements were identified in 19 of 47 and 29 of 47 patients, respectively.A stronger bias at the level of both IGHV and IGKV gene was observed with IGHV4-34in 8/19 (42.1%) and IGKV4-1 in 19/29 (65.5%) cases respectively. The majority(45/50, 90%) of IgHV and IgLV genes were mutated. Two cases had an identicalheavy chain CDR3 (HCDR3) sequence and another two cases had another identicalHCDR3 sequence. Nineteen of 27 (70.5%) kappa chain CDR3 (KCDR3) sequences werehighly homologous and met the criteria for stereotyped rearrangements and 14 ofthe 19 sequences were identical. A specific combination of IGKV4-1 and IGKJ4usage was also observed in these 19 patients. Notably, the HCDR3 sequencesexhibited a high homology to antibodies specific for HBsAg in 15 of 16patients, and for HBcAg in the remaining one patient. The KCDR3 sequences in 28of 29 patients (96.6%) and the lambda chain CDR3 (LCDR3) sequences in 2patients also showed the highest homology to antibodies specific for HBsAg. Conclusion:We conclude that HBV-associated DLBCL might arise from HBV antigen-selectedB cells and antigen stimulation might play an important role in thepathogenesis of these lymphomas.

Key Words: Hepatitis B virus  diffuse large B cell lymphoma