(A) Assay concept: (Left) cells expressing CD32B and SHIP-1 with
complementary SmBiT and LgBiT fusions, respectively, and CD32A with no fusion.
(Middle) Following stimulation with IC, SHIP-1 is recruited to the
phosphorylated (P) ITIM of CD32B, leading to interactions between LgBiT and
SmBiT fragments to form complete NanoLuc enzymes. (Right) In the presence of a
NanoLuc substrate, complete luciferase enzymes produce luminescence, reflecting
SHIP-1 recruitment to CD32B. NB: Monomeric IgG, being unable to crosslink
FcγRs, is not expected to induce SHIP-1 recruitment, resulting in no
increase in luminescence. (B-C) HEK293F cells, transiently
co-transfected with CD32B-SmBiT and SHIP-1-LgBiT (C-terminus) alone (B) or with
CD32A (C) on d0, were stimulated with medium, IC or monomeric IgG
(10µg/ml) on d1. Luminescence readings were taken at time 0 following
substrate addition, and at 5 minute intervals following stimulation. Responses
are shown as (top) relative luminescence units (RLU) or (bottom) fold inductions
of response relative to medium control (fold induction). Means ± S.D. of
technical replicates are shown. (D) Mean fold inductions (at 15
minutes) from repeat experiments where cells were co-transfected as in (C) and
treated with monomeric IgG or IC on d1, as above (n=4 experiments). Statistical
significance between groups was assessed using a 2-way ANOVA with Tukey’s
multiple comparisons test. **** – p<0.0001; n.s. –
not-significant.