B cell hyperactivity is a common immune abnormality in ARC and AIDS and may represent a major predisposing factor leading to the development of B cell lymphomas. The cause for this B cell hyperactivity is not completely understood at this time, but impaired T cell function, B cell dysregulation and massive EBV infection are likely to be important contributing factors. The monokines, IL-1 alpha, IL-1 beta, IL-6 and a novel 6-9 K MW factor, are increased in mononuclear cell (PBM) cultures from patients with AIDS and in vitro HIV infection of normal macrophages. Among their other activities, these monokines stimulate B cell growth and/or Ig production. The long term objective of this proposal is to evaluate the role of these monokines in B cell hyperactivity in AIDS.
The specific aims are: I. To characterize the interaction of IL-l alpha, IL-l beta, IL- 6,and the 6-9 K MW factor on HIV-infected and uninfected EBV- transformed B cells. Production and release of these factors by infected and uninfected EBV cell lines will be determined by chromatographic separation, testing for the factors by bioassay, neutralization of bioactivity with specific antibodies, immunoassay, and Northern blot analysis. The effect of these monokines on growth and Ig production of HIV infected and uninfected EBV cell lines will be determined. The effect of these factors on the susceptibility of normal B cells to EBV transformation will be determined by limiting dilution analysis. II. To characterize the mode of action of 6-9 K MW factor on normal B cells. The effect of this factor on resting, Staphylococcus aureus Cowan strain I (SAC) induced B cell proliferation and Ig production, and dependence on or synergy with IL-l alpha, IL-l beta, IL-6 and other known B cell factors will be determined. The contribution of T cells and M0 will be assessed. The effect of these factors on B cell subpopulations will be determined.
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