Interleukin 4 instructs uncommitted B lymphocytes to switch to IgG1 and IgE

Mouse interleukin 4 (IL 4) is a T cell-produced lymphokine with multiple effects on different cells types of the hematopoietic lineages. IL 4 has pronounced effects on B lymphocytes, where it induces high levels of IgG1 and IgE secretion in lipopolysaccharide-stimulated cultures that would otherwise secrete predominantly IgG3 and IgG2b (of the non-IgM isotypes). An important question is how IL 4 exerts its effect. Two main possibilities exist: (a) IL 4 instructs uncommitted B lymphocytes to IgG1 and IgE production; (b) IL 4 selects and expands an already precommitted B cell. In this study we show, by the use of limiting dilution analysis, that IL 4 dramatically increases the precursor frequency of IgG1 and IgE-secreting cells with no significant effect on the clone size, clearly suggesting that IL 4 instructs uncommitted B cells to switch to IgG1 and IgE. The fraction of total Ig precursors that can switch to the two isotypes is furthermore high. The high precursor frequency for IgE obtained in the presence of IL 4 further demonstrates that IL 4 is an important modulator of IgE responses.