B1 AND B2 CELLS DIFFER IN THEIR POTENTIAL TO SWITCH IMMUNOGLOBULIN ISOTYPE

The ability of purified Bla (Ly-1 B) and B2 cells to switch immunoglob ulin isotype was assessed by limiting dilution analysis in two in vitr o culture systems. When stimulated in the presence of interleukins-4 a nd -5 by either lipopolysaccharide or CD40 ligand, the frequency of Ig G 1 precursors in the Bla population was at most one third that of IgM precursors. In B2 cells, however, the frequency of IgG1 precursors wa s up to seven times that of IgM precursors. Bla cells were shown to re spond to interleukin-4 by virtue of up-regulating major histocompatibi lity complex class II expression when exposed to the cytokine, preclud ing non-responsiveness as a reason for not switching to IgG1. Indeed, interleukin-4 was found to specifically induce transcription of the ge rm-line IgG1 constant region locus in Bla cells as it did in B2 cells. Collectively these results suggest that the ability of B1 cells to re spond to isotype switch commitment factors such as interleukin-4 may b e secondary to the production of IgM by these cells.