The mechanisms of activation, proliferation and differentiation of human B cells were studied at the cellular and molecular levels. A T cell-derived B cell activating factor was identified which directly activated resting human B cells. A high molecular weight B cell growth factor (HMW-BCGF) which we had previously described was shown to induce c-myc expression in resting B cells in the absence of subsequent proliferation. The receptor for HMW-BCGF was identified and characterized on human B cells. This constitutes the first description of a B cell growth factor receptor. Separate clones derived from a B cell lymphoma were shown to selectively produce or respond to BCGF. The precise role of interleukin 2 (IL-2) and IL-2 receptors in B cell function were studied and the selective effect of IL-2 versus B cell differentiation factor on human B cells was demonstrated to depend on the state of maturation of the responding cell. The effects of complement components and fibronectin proliferation on the differentiation of human B cells were described. Metabolites of arachadonic acid such as leukotriene C4 and prostaglandin E2 were shown to have profound effects on B cell function indicating an important link between the inflammatory response and B cell function. Abnormalities of BCGF receptor formation were described in patients with common variable hypogammaglobulinemia constituting the first recognition of an abnormality at the level of interaction between BCGF and its receptor in a human disease. The pharmacologic modulation of the human immune response was studied, particularly with regard to the effects of corticosteroids, cyclosporin A, and certain neuropeptides on distinct phases of the human B cell cycle.
