The switch from IgM to IgG (or IgA, IgE) synthesis has been studied in both normal and neoplastic Ig-secreting cells (1-6). Evidence suggests that DNA rearrangements precede isotype switching. The nature of the signals that induce isotype switching are not understood, although T cells (7-13), T cell-derived lymphokines (14)(15)(16)(17)(18)(19)(20), and mitogens (20-22) can influence switching in activated B cells.We have previously (16) described a T cell-derived lymphokine termed "B cell differentiation factor for IgG" (BCDF3,), l that induces increased levels of IgG1 secretion in lipopolysaccharide (LPS)-stimulated splenic B cells. T cell supernatants (SN) containing BCDF3, also contain lymphokines that suppress the secretion of IgG3 (23) and IgG2 (24,25). These changes in IgG secretion are accompanied by corresponding changes in the steady state levels of mRNA for each IgG subclass (23). BCDF3,-containing SN do not act on cells that bear surface IgG (sIgG) at the initiation of culture (16). Furthermore, BCDF7 does not bind to Sepharose-coupled IgM, IgD, or IgG (25). The cell surface receptor for BCDF3,, then, is probably not sIg.The mechanism of action of BCDF3, is unclear. It might induce growth of an sIgG + subset of B cells. Alternatively, BCDF3" might induce sIgG-B cells to secrete IgG1. In the present studies, we have examined the effects of a BCDFTcontaining T cell SN on normal B cells in a limiting dilution culture system. Our results suggest that BCDF3,-containing SN induce IgG1 secretion in a subset of sIgG-B cells already committed to a differentiation pathway leading to IgG1 secretion. These cells do not arise from precursors of IgG3-secreting cells.
Materials and MethodsAnimals. We used female C57BL/6 × DBA/2 F~ (BDF1) mice (The Jackson Laboratory, Bar Harbor, ME) 8-16 wk old. Lewis rats (Harlan Sprague Dawley, Inc., Indianapolis, IN), used at 3-6 wk, were a source of thymus cells.