High-affinity mAbs restrict BG18gH responses in an epitope-dependent manner
(A) Schematic of experiment to evaluate the effects of i.v. administration of monoclonal antibodies on naive BH18gH B cell responses in WT recipients.
(B and C) (B) GC cells as the percentage of total B cells and (C) CD45.2+ BG18gH cells as the percentage of total GC B cells at 10 dpi in BG18gH recipients receiving 30 μg of either high-affinity murine IgG1 BG18 mAb (BG18_d42.10, green) or high-affinity human IgG1 BG18 mAb (BG18_iGL0, red).
(D) CD45.2+ BG18gH cells as the percentage of total GC B cells at 10 dpi of BG18gH recipients receiving escalating concentrations of the high-affinity BG18_iGL0 mAb.
(E) CD45.2+ BG18gH cells as the percentage of total GC B cells at 10 dpi of BG18gH recipients receiving 10 μg of BG18 mAbs with increasing affinity for the N332_GT2 immunogen (BG18_Pre5 with KD 1.3μM, BG18_Pre14 with KD 93 nM, and BG18_iGL0 with KD 4 nM).
(F) Schematic of the HIV Env trimer and binding sites of the bnAbs used in (G)–(J).
(G and H) (G) GC cells as the percentage of total B cells and (H) CD45.2+ BG18gH cells as the percentage of total GC B cells at 10 dpi in BG18gH recipients receiving 10 μg of the BG18-epitope binding mAbs BG18_iGL0 and PGT128.
(I and J) (I) GC cells as the percentage of total B cells and (J) CD45.2+ BG18gH cells as the percentage of total GC B cells at 10 dpi in BG18gH recipients receiving 10 μg of antibodies binding other epitopes on the N332-GT2 immunogen.
p values were calculated by ordinary one-way ANOVA with Dunnett’s multiple comparisons (∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001; ns, not significant). Figures represent data from one of at least two experiments with 3–5 mice per condition, with data presented as mean ± SD.