Assessment of responses of normal human B lymphocytes to different isolates of human immunodeficiency virus: role of normal donor and of cell line used to prepare viral isolate.
The effect of different HIV-1 isolates on normal human B lymphocyte function has been studied in vitro. Production of IgM and IgG was measured by ELISA using a "standard" non-T preparation of B cells depleted of macrophages and T cells (but not of low-density accessory cells, LDC). Only one (H9/CBL-4) of five different isolates induced polyclonal production of immunoglobulin. Apart from intrinsic differences between isolates, important inherent variables were shown to affect the response. One was the mix of cell types in the responding preparation of B cells. This was tested by examining the effects of HIV-1 isolates independently on the accessory function of LDC and on B cell function when the LDC were removed. Isolate H9/HTLV-IIIRf was nonstimulatory on a B cell preparation containing LDC and suppressive on LDC accessory function yet could enhance function of B cells when the LDC were depleted. Another variable was the donor of the normal B cells. The B cell response was consistent with each donor but varied greatly with different donors. Thus, no single explanation emerges for the hypergammaglobulinemia in some adult AIDS patients and for the hypogammaglobulinemia in some pediatric cases. Additionally, the cell lines used to propagate the virus particularly affected the assay of B cells depleted of LDC. Uninfected supernatants had different effects on the B cell function, and these host cell effects (perhaps by release of cytokines or other mediators) may be exacerbated in infected cell lines. Our data show the complexity of the abnormal B cell function in AIDS.