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. Author manuscript; available in PMC: 2015 Jul 22.
Published in final edited form as: Nature. 2014 Nov 2;517(7535):501–504. doi: 10.1038/nature13868

Figure 4. Ag-specific IgG1 prevents IgG3-mediated glomerulopathy.

Figure 4

BALB/c γ1- mice (5/gp) were injected with GaMD on day 0 and/or GaMD-immune or rabbit anti-mouse IgD (RaMD) immune WT serum daily on d4-7. a,b, Urine protein (a) and d12 serum albumin and BUN levels (b). * p<0.05, **p<0.005, NS = not significant. c, BALB/c γ1- mice (5/gp) were injected with GaMD on d0 ± GaMD immune WT serum daily on d4-7 or 5-7. Spleens were harvested and cultured on d8; 24 hr culture supernatant IgG2a, IgG3, and IgM anti-goat IgG titers were determined. No anti-goat IgG Ab was detected in culture supernatants from non-immune spleen cells. d, WT and C3-deficient (C3-) mice (4/gp) were injected s.c. with 100 μl of TNP-goat serum and i.v. with 4 mg of mouse IgG3 anti-TNP ± 5 mg of IgG1 anti-TNP mAbs on d0 and 1. Urine was analyzed on d0, 1 and 2. e, WT and FcγRIIB-deficient (FcγRIIB-) mice (4/gp) were injected s.c. with 100 μl of TNP-goat serum and i.v. with 4 mg of IgG3 anti-TNP ± 5 mg of IgG1 anti-TNP on d0 and 1. Urinalysis on d0, 1 and 2. f, BALB/c mice were injected i.v.with 4 mg IgG3 anti-TNP and s.c. with 1.4 mg of TNP-BSA on days 0 and 1. Some mice were also injected with 0.625, 1.25, 2.5, or 5 mg of switch variant IgG1, IgG2a or IgG2b anti-TNP mAbs on d0 and 1. Urine protein was determined on d0 (not shown), d1 (upper panel) and d2 (lower panel). Results are pooled from a total of 7 experiments. Group size: IgG3 alone: 19 mice; 0.625 mg of IgG1, IgG2a, or IgG2b: 4 mice; 1.25 mg of IgG1, IgG2a or IgG2b: 8 mice; 2.5 mg of IgG1, IgG2a or IgG2b: 6 mice; 5 mg of IgG1, IgG2a or IgG2b: 8 or 9 mice. The significance of differences between treatment groups was determined with a normal regression model with the covariates: group, dose and group-dose interaction; a t-test was used to evaluate the significance of the difference in least square means for each of these effects. This procedure was used to evaluate urine protein, measured at day 1 and day 2. A p-value less than or equal to 0.05 after applying the Tukey adjustment for multiple comparisons was judged to be significant. # p<0.05 as compared to IgG2a plus IgG3. +p<0.05 as compared to IgG2b plus IgG3. *p<0.05 as compared to IgG3 alone.