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• W2031562389 abstract "The pathogenesis of polyclonal HIV-associated lymphomas lacking traditional B cell cofactors (i.e., Epstein-Barr virus [EBV] infection, c-myc translocations) is poorly understood. A multistep pathogenesis model has been proposed in which polyclonal lymphomas represent an earlier stage in HIV-associated lymphomagenesis before the emergence of a dominant malignant clone. Chronically present antigens have been proposed as a likely stimulus for polyclonal B cell proliferation; if so, polyclonal lymphoma--associated immunoglobulins (Igs) should have molecular evidence of somatic hypermutation, a process by which antibody affinity maturation in response to chronic antigenic stimulation occurs. Molecular analyses of Ig heavy chain variable (VH) gene use by B cells in a polyclonal HIV-associated large cell lymphoma lacking EBV and c-myc rearrangement was undertaken. Eighteen randomly selected clones generated from RT-PCR yielded 15 unique VH sequences, all of which were most homologous to only three previously identified germline VH1 genes. Two sets of clones (consisting of three and two clones, respectively) had identical VH gene sequences, and one pair of clones had identical third complementarity determining regions (CDR3s) but different VH gene sequences; eight clones were <95% homologous to their most related germline VH1 genes. We compared these results with Ig VH1 gene use by B cells present in a reactive hyperplastic lymph node obtained from an HIV-1-infected individual. Fifteen clones randomly selected from RT-PCRs yielded 15 unique VH1 sequences, all of which were most homologous to 5 previously identified germline VH1 genes; 10 clones were <95% homologous to their most related germline gene. Binomial probability analysis revealed that only 1 of the 15 unique VH1 sequences derived from the polyclonal lymphoma (i.e., 7%), as compared with 5 of 15 unique VH1 sequences derived from the reactive lymph node (i.e., 33%), had a low probability of occurrence by random chance (p <0.05). These data provide molecular evidence of polyclonality in an HIV-associated polyclonal lymphoma, demonstrate a qualitative difference in somatic hypermutations of Ig VH genes associated with malignant versus reactive B cell lymphoproliferations, and support an antigen-mediated multistep pathogenesis model of HIV-1-associated lymphomagenesis." @default.
• W2031562389 created "2016-06-24" @default.
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• W2031562389 date "1997-01-20" @default.
• W2031562389 modified "2023-09-27" @default.
• W2031562389 title "V_HGene Use by HIV Type 1-Associated Lymphoproliferations" @default.
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• W2031562389 doi "https://doi.org/10.1089/aid.1997.13.135" @default.
• W2031562389 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9007199" @default.
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