FIGURE 4.

p110δ is the primary PI3K isoform that contributes to B cell proliferation. A, anti-IgM-mediated B cell proliferation from three independent experiments was normalized to a percentage scale. Concentrations used were MLN1117 and A66 (0.25, 0.5, 1, and 2 μm), TGX-221 (0.25, 0.5 μm), MLN1316 (0.25, 0.5, and 1 μm), GDC-0941 (0.25 and 0.5 μm), and IC87114 (0.5 and 1 μm). B, anti-IgM + IL4-mediated B cell proliferation from three independent experiments was normalized to a percentage scale. Concentrations used were MLN1117, A66, and MLN1316 (0.5, 1, and 2 μm), TGX-221 (0.5 μm), GDC-0941 (0.5 μm), and IC87114 (1 μm). C, anti-IgD + IL-4-mediated human B cell proliferation from three independent experiments was normalized to a percentage scale. Concentrations used were MLN1117 (0.5, 1, and 2 μm), GDC-0941 (0.5 μm), and IC87114 (1 μm). D, three independent experiments of LPS-mediated B cell proliferation were analyzed in a similar manner to B. 1 μm concentration was used for all inhibitors except GDC-0941 (0.5 μm) and TGX-221 (0.5 μm). In the combination treatments, IC87114 (1 μm) with 1 μm of the indicated inhibitors was used. All data represent results from at least three independent experiments (*, p < 0.05; **, p < 0.005; ***, p < 0.001, repeated-measures analysis of variance, measured versus the untreated control).