We measured the plasma levels of B-lymphocyte stimulator (BLyS) in 101 HIV-1-infected patients and 18 controls. BLyS levels were higher among HIV-positive patients [median 5.70 (3.90) versus 4.62 (1.04) ng/ml, P 0.002], who had significantly higher BLyS and total serum globulin levels with decreasing CD4 cell counts. Moreover, BLyS levels increased exponentially below 100 CD4 cells/ìl. BLyS and globulin levels increase as HIV disease progresses, suggesting a role for BLyS in the hypergammaglobulinemia of HIV infection.

HIV infection is often accompanied by polyclonal hypergammaglobulinemia [1–5], resulting from a state of generalized, non-specific B-cell activation [6–8]. The mechanism underlying this phenomenon has not been conclusively established. B-lymphocyte stimulator protein (BLyS) is a member of the tumor necrosis factor ligand superfamily that regulates the survival, proliferation and differentiation of B lymphocytes [9–13]. In vitro, BLyS induces B-cell activation and expansion [12, 14]; in vivo, exogenous administration of BLyS to mice leads to the expansion of B-cell populations in lymphoid tissue and increased serum immunoglobulin levels [11, 12]. In humans, BLyS levels are elevated in autoimmune disorders associated with hypergammaglobulinemia [15–18] and in follicular non-Hodgkin’s lymphoma [17]. Given the similarities between the biological actions of BLyS and the humoral immune derangements seen in HIV infection, we hypothesized that BLyS levels may be abnormal in HIV disease.