Abstract
The chronic lymphocytic leukemia (CLL) immunoglobulin repertoire is uniquely characterized by the presence of stereotyped B-cell receptors (BCRs). A major BCR stereotype in CLL is shared by immunoglobulin G-switched cases utilizing the immunoglobulin heavy-chain variable 4-34 (IGHV4-34) gene. Increased titers of IGHV4-34 antibodies are detected in selective clinical conditions, including infection by B-cell lymphotropic viruses, particularly Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In this context, we sought evidence for persistent activation by EBV and CMV in CLL cases expressing the IGHV4-34 gene. The study group included 93 CLL cases with an intentional bias for the IGHV4-34 gene. On the basis of real-time PCR results for CMV/EBV DNA, cases were assigned to three groups: (1) double-negative (59/93); (2) single-positive (CMV- or EBV-positive; 25/93); (3) double-positive (9/93). The double-negative group was characterized by heterogeneous IGHV gene repertoire. In contrast, a bias for the IGHV4-34 gene was observed in the single-positive group (9/25 cases; 36%). Remarkably, all nine double-positive cases utilized the IGHV4-34 gene; seven of nine cases expressed the major BCR stereotype as described above. In conclusion, our findings indicate that the interactions of CLL progenitor cells expressing distinctive IGHV4-34 BCRs with viral antigens/superantigens might facilitate clonal expansion and, eventually, leukemic transformation. The exact type, timing and location of these interactions remain to be determined.
Original language | English |
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Pages (from-to) | 919-24 |
Number of pages | 6 |
Journal | Leukemia |
Volume | 23 |
Issue number | 5 |
DOIs | |
Publication status | Published - May 2009 |
Externally published | Yes |
Keywords
- Aged
- B-Lymphocytes/immunology
- Case-Control Studies
- Cohort Studies
- Cytomegalovirus/physiology
- Disease Progression
- Female
- Genome, Viral
- Herpesvirus 4, Human/physiology
- Humans
- Immunoglobulin Heavy Chains/genetics
- Immunoglobulin Variable Region/genetics
- Leukemia, Lymphocytic, Chronic, B-Cell/genetics
- Male
- Middle Aged
- Receptors, Antigen, B-Cell/genetics
- Reverse Transcriptase Polymerase Chain Reaction
- Somatic Hypermutation, Immunoglobulin
- Time Factors
- Virus Activation