Regulation of B cell activation and differentiation with factors generated by human T cell hybridomas.

Human T cell hybridomas were generated by several techniques and the supernatants generated were screened for activity on human B cells. Three general activities were noted; B cell proliferation factor ( BCPF ), B cell differentiation factor (BCDF), and an IgA isotype-specific helper factor. BCPF acts on B cells to induce proliferation without differentiation and is distinct from conventional BCGF. This was documented by BCPF 's inability to synergize with anti-mu Ab in a standard BCGF assay ( Muraguchi & Fauci 1982, Howard et al. 1982, Sieckman et al. 1981), as well as its differential effect on a leukemic B cell preparation, when compared with BCGF. A possible schema for BCPF activity is depicted in Figures 3 and 4. In Figure 3, BCPF acts like Ag in vivo or like anti-mu in vitro, pre-activating B cells and rendering them responsive to BCGF. Figure 4 represents what our data depict, that is that BCPF bypasses the response to BCGF and induces cells to proliferate without pre-activation. The difference in the 2 mechanisms may be concentration-dependent and this possibility is currently being evaluated. It is interesting to speculate that T cells in vivo are capable of initiating B cell activation and may account for polyclonal responses seen with some Ag-specific reactions. BCDF(s) act on post-activated B cells (Figure 3) to induce differentiation to Ig-secreting cells. They appear to be heterogeneous and, therefore are capable of inducing varied responses depending on the B cell subpopulation affected. Figure 3 is deliberately complex demonstrating some of the possible as well as documented BCDF activities including polyclonal differentiation and isotype specific activity in IgA committed B cells. We cannot be certain of the frequency of these BCDF-secreting T cells, but the studies of cells from patients with common variable immunodeficiency and chronic lymphocytic leukemia have helped to dissect out these activities. These data would suggest that these BCDF subgroups are important, as deficiencies in one or more subgroups may result in disease.