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

Primary effusion lymphoma (PEL) is a lymphoproliferation of B cells infecte d by Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8 and reflec ting a late stage of B cell differentiation close to plasma cell. Apart fro m viral infection, the pathogenesis of PEL is currently unclear. The aim of the present study was to investigate the role of antigen stimulation and s election 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 l ight chain isotypes expressed by these lymphomas, immunoglobulin (Ig) genes from seven AIDS-related PEL were sequenced (three cell lines and four prim ary samples). Most of the samples (five out of seven) used lambda light cha in genes; the majority of these (n = 4) belonged to the V lambda 3 family. Two cases expressed mu chains, whereas gamma chains were found in two cases . In all cases, significant deviations from the presumed germline counterpa rt 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. Ev idence for selection was more frequent in the light chain genes than in the heavy chain genes. Collectively, these data indicate that PEL originate fr om mature, antigen-experienced B cells and bear implications for the pathog enesis and histogenesis of this lymphoma.