Human immunodeficiency virus-associated Hodgkin's disease derives from post-germinal center B cells

Human immunodeficiency virus-associated Hodgkin's disease (HIV-HD) displays several peculiarities when compared with HD of the general population. The se include overrepresentation of clinically aggressive histologic types and frequent infection of Reed-Sternberg (RS) cells by Epstein-Barr virus (EBV ). Recently, we have reported that the histogenesis of HD of the general po pulation may be assessed by monitoring the expression pattern of BCL-6, a t ranscription factor expressed in germinal center (GC) B cells, and of CD138 /syndecan-l (syn-l), a proteoglycan associated with post-GC, terminal B-cel l differentiation. In this study, we have applied these two markers to the study of HIV-HD histogenesis and correlated their expression status to the virologic features of this disease. We have found that RS cells of all hist ologic categories of HIV-HD consistently display the BCL-6(-)/syn-1(+) phen otype and thus reflect post-GC B cells. Although BCL-6(-)/syn-1(+) RS cells of HIV-HD express CD40, they are not surrounded by CD40 ligand-positive (C D40L(+)) reactive T lymphocytes, which, in HD of the general population, ar e thought to regulate the disease phenotype through CD40/CD40L interactions . Conversely, RS cells of virtually all HIV-HD express the EBV-encoded late nt membrane protein 1 (LMP1), which, being functionally homologous to CD40, may contribute, at least in part, to the modulation of the HIV-HD phenotyp e. (C) 1999 by The American Society of Hematology.