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It has been demonstrated from several laboratories that there exists a number of antigen-nonspecific soluble factors that can transmit signals for growth and/or differentiation among various types of leukocytes and that thus play a potentially major role in the regulation of immune responses (1, 2). Certain studies have demonstrated that monocyte-derived interleukin 1 (IL-1) 1 induces certain thymusderived T cell subsets to secrete IL-2, which in turn can maintain the continuous in vitro proliferation of other T cell subsets (3, 4). In this regard, by using IL-2, it has recently become possible to maintain the long-term culture of antigen-specific mouse or human T cell clones (5-10).Compared with the use of IL-1 and IL-2 in T cell systems, the modulation of bone marrow-derived B cell activation, proliferation, and differentiation by soluble factors is poorly understood. Recent studies of the long-term culture of normal mouse and human B cells have indicated the existence of T cell-derived B cell growth factors (BCGF) that deliver signals to activated B cells to maintain a proliferative state (11-13). Indeed, we and others have reported that there are separate signals required for B cell proliferation vs. differentiation in both the mouse and human models (14)(15)(16)(17).With regard to the sources of human BCGF, we have recently demonstrated that substantial BCGF activity was contained in culture supernatants of phytohemagglutinin (PHA)-stimulated human mononuclear cells (MNC) (18) and that BCGF and IL-2 elaborated by mitogen-stimulated peripheral blood T cells are separate molecules (19). Finally, we have most recently developed a human T-T hybridoma that produces BCGF in the absence of other demonstrable T cell factor activity (20). In the present study, using this monoclonal BCGF, we have examined the various activation signals required by purified human peripheral blood or tonsillar B cells for proliferative responses to BCGF. The data strongly suggest that there are at least two subsets of human B cells with regard to their relative susceptibility to proliferative signals delivered by BCGF, based on their state of in vivo activation.

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