Immunoglobulin V region gene use and structure suggest antigen selection in AIDS-related primary effusion lymphomas

Abstract

Primary effusion lymphoma (PEL) is a lymphoproliferation of B cells infected by Kaposi’s sarcoma-associated herpes- virus/human herpesvirus-8 and reflecting a late stage of B cell differentiation close to plasma cell. Apart from viral infection, the pathogenesis of PEL is currently unclear. The aim of the present study was to investigate the role of antigen stimulation and selection in the evolution of PEL. In order to assess the specific variable heavy (V_H) and light (V_L) genes used by PEL and to define the heavy and light chain isotypes expressed by these lymphomas, immunoglobulin (Ig) genes from seven AIDS-related PEL were sequenced (three cell lines and four primary samples). Most of the samples (five out of seven) used lambda light chain genes; the majority of these (n = 4) belonged to the V lambda 3 family. Two cases expressed μ chains, whereas γ chains were found in two cases. In all cases, significant deviations from the presumed germline counterpart were found in both the expressed V_H and V_L genes. Statistical evidence for antigen selection was evident in four out of seven samples studied. Evidence for selection was more frequent in the light chain genes than in the heavy chain genes. Collectively, these data indicate that PEL originate from mature, antigen-experienced B cells and bear implications for the pathogenesis and histogenesis of this lymphoma.