Fig. 3: SCFAs reduce class-switched and hypermutated T-dependent and T-independent antibody responses. | Nature Communications

Fig. 3: SCFAs reduce class-switched and hypermutated T-dependent and T-independent antibody responses.

From: B cell-intrinsic epigenetic modulation of antibody responses by dietary fiber-derived short-chain fatty acids

Fig. 3

a–d C57BL/6 mice fed fiber diet on SCFAs water (SCFAs) or plain water (Nil) starting at the age of 5 weeks, and i.p. injected with NP16-CGG (in Alum) or NP-LPS (in PBS) at the age of 8 weeks. The mice were boost-injected 3 weeks later with NP16-CGG or NP-LPS, respectively, and killed a week after the boost injection. a, b Titers of total and NP3-binding serum IgM, IgG1, and IgA in NP16-CGG injected C57BL/6 mice (a), as well as total and NP3-binding serum IgM, IgG3, and IgG2b titers in NP-LPS injected C57BL/6 mice (b), as measured by ELISA (n = 4 per group, pooled from two experiments). Bars represent the mean ± SD. c, d Somatic point mutations in the V186.2 regions from V186.2DJH-Cγ1 transcripts of NP16-CGG injected C57BL/6 mice (c), or from V186.2DJH-Cγ3 transcripts of the NP-LPS injected C57BL/6 mice (d). Sequence data were pooled from three mice in each group. Pie charts depict the proportions of sequences that carry different numbers of point mutations; listed below the pie charts is the overall mutation frequency (change/base). Donut charts depict the spectrum of point mutations. e–h Tcrβ–/–Tcrδ–/– mice on SCFAs water or plain water were injected with NP-LPS. Total and NP3-specific serum IgM, IgG3, and IgG2b titers were measured by ELISA (n = 5 per group) (e). Somatic point mutations in the V186.2 region of V186.2DJH-Cγ3 and V186.2DJH-Cγ2b transcripts. Sequence data were pooled from three mice in each group (f). AID and Blimp1 expression in spleen B cells of these mice, AID expression in spleen B cells of Aicda-/- mice, and Blimp1 expression in naive B cells of C57BL/6 mice, as analyzed by intracellular staining followed by fluorescence microscopy (g), and flow cytometry (h). Data in g and h are representative of three independent experiments. i Quantification of AID+ and Blimp1+ cells in h and g. n = 3 per group. *p < 0.05, **p < 0.01, ***p < 0.001 (unpaired t test). Scale bar = 10 μm. The source data are provided in Source Data file.

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