Distinct Kinds of B Cell Growth Fac tor and Thei r Synergism in B Cell Proliferation

Discovery and use o f T cell growth factor, interleukin 2 (IL-2), 1 have made it possible to immortalize functioning T cells and have facilitated studies on the activation, function, and antigen recognition of T cells (1-3). Human and murine neoplastic T cells secreting IL-2 have been particulary useful for the isolation and molecular characterization of IL-2 (4, 5). Recent studies with successful long-term culture of murine or human B cells (6, 7) as well as with short-term B cell culture (8) have suggested the requirement of T cellderived growth factor(s) for maintaining the continuous proliferation of activated B cells. Our studies with human leukemic B cells also showed that anti-immunoglobulin (anti-Ig) and growth factor were required for proliferation of B cells and three signals, anti-Ig, growth factor, and differentiation factor, were required for Ig production (9). However, little is known about B cell-specific growth factor (BCGF), and the lack of homogeneous BCGF preparations without IL-2 activity has hampered the establishment of nontransformed B cell lines. Previously, we showed the successful establishment of stable human T hybridomas secreting several monoclonal immunoregulatory molecules involved in the proliferation and differentiation of T cells, such as IL-2 or killer helper factor(s) (10). In the present study, we used a similar method for obtaining homogeneous factors involved in the proliferation or differentiation of B cells. T hybridomas secreting BCGF or B cell differentiation factor (BCDF) have been established, and the results show the presence of molecular and functional heterogeneity in BCGF and the synergistic effect of two distinct kinds of BCGF on the proliferation of B cells. The results also show that BCDF involved in the final differentiation of B cells into Ig-producing cells is different from BCGF or IL-2. By using these monoclonal factors, activation process of B cells into Ig-producing cells are able to be dissected and reconstituted in vitro.