Evidence for a Mesothelial Origin of Body Cavity Effusion Lymphomas

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Abstract

Background: Primary effusion lymphoma (PEL) is a Kaposi's sarcoma herpes virus (KSHV)–induced lymphoma that typically arises in body cavities of HIV-infected patients. PEL cells are often co-infected with Epstein-Barr virus (EBV). “PEL-like” lymphoma is a KSHV-unrelated lymphoma that arises in body cavities of HIV-negative patients. “PEL-like” lymphoma is sometimes EBV positive. The derivation of PEL/“PEL-like” cells is unclear.

Methods: Mesothelial cells were cultured from body cavity effusions of 23 patients. Cell proliferation, cytokine secretion, marker phenotypes, KSHV/EBV infection, and clonality were evaluated by standard methods. Gene expression was measured by quantitative polymerase chain reaction and immunoblotting. A mouse model of PEL (3 mice/group) was used to evaluate tumorigenicity.

Results: We found that the mesothelia derived from six effusions of HIV-infected patients with PEL or other KSHV-associated diseases contained rare KSHV+ or EBV+ mesothelial cells. After extended culture (16–17 weeks), some mesothelial cells underwent a trans-differentiation process, generating lymphoid-type CD45+/B220+, CD5+, CD27+, CD43+, CD11c+, and CD3− cells resembling “B1-cells,” most commonly found in mouse body cavities. These “B1-like” cells were short lived. However, long-term KSHV+EBV− and EBV+KSHV− clonal cell lines emerged from mesothelial cultures from two patients that were clonally distinct from the monoclonal or polyclonal B-cell populations found in the patients’ original effusions.

Conclusions: Mesothelial-to-lymphoid transformation is a newly identified in vitro process that generates “B1-like” cells and is associated with the emergence of long-lived KSHV or EBV-infected cell lines in KSHV-infected patients. These results identify mesothelial cultures as a source of PEL cells and lymphoid cells in humans.

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