T cell dependent B lymphocyte activation, growth and maturation the role of lymphokines

Sammanfattning: The present work concerns the regulation of B cell activation, growth and terminal differentiation of helper T cells.T cell dependent (TD) B cell activation requires physical cell to cell contact between competent helper T cells (TH) and B cells and the recognition of MHC Class II antigens. The involvement of immunoglobulin receptors in TD B cell induction and maturation of B cells to plasma cells, however, are still unclear.Long term helper T cell lines and clones were raised against naturally expressed minor transplantation antigens. Using such antigen specific TH lines and clones, the mechanisms controlling growth and maturation of B cells to plasma cells were studied. Specific TH cells against both H-Y and C3H/Tif "minor" antigens were able to polyclonally induce small, resting B lymphocytes to proliteration and high rate antibody secretion. This observation definitively excludes an obligatory role of membrane immunoglobulin molecules in TD B cell triggering.In contrast to other similarly derived TH clones, a variant clone, was isolated which was fully competent to activate B cells to proliferation but did not induce PFC in T cell depleted "target" spleen cells. This defect could, however, be fully reconstituted by cell culture supernatants derived from competent TH clones (but not from the variant clone). These results indicated the presence of two distinct factors in such supernatants, controlling either growth or maturation in TD B cell responses, and lead to further efforts in their characterization. A B cell growth factor (BSF-pI) derived from such supernatants, with a Mr of 15-20 kD, displayed no mitogenicity on small, resting B lymphocytes and failed to induce PFC in prol iterating B cells. On the other hand, two distinct species of B cell maturation factors (BMA) were separated from the supernatants with Mr of 60 kD and 30 kD, respectively. These factors induced PFC of several antibody isotypes in assays were only maturation activity was limiting, but only the 60 kD species induced Ig-secretion, in pure populations of lymphoma cells (WEHI-279.1).Finally, neonatal B cells were shown to be inducible to growth but not to immunoglobulin secretion by competent TH cells, in the absence of suppressive effects in the neonatal spleen cell population. These results suggest that "early" B lymphocytes are intrinsically defective in the reception or processing of maturation signals.