Panel A: A vertical bar graph compares serum I g D levels in adult and pediatric healthy controls and various P I D or H I D S patients. The y-axis represents serum I g D levels in micrograms per milliliter, and the x-axis lists different patient groups. Some data points are below the limit of detection, indicated by gray symbols. Panel B: Another vertical bar graph shows serum I g D levels in specific P I D patients, with the y-axis representing serum I g D levels and the x-axis listing different patient groups. Panel C: A vertical bar graph compares serum I g D levels in H I D S, C A R D 11, and C D G patients, with the y-axis representing serum I g D levels and the x-axis listing different patient groups. Panel D: A scatter plot shows the correlation between age and the frequency of tonsillar I g D-P C s in healthy controls, with the y-axis representing the percentage of I g D-P C s and the x-axis representing age. Panel E: A scatter plot shows the correlation between age and the frequency of I g D-M E B cells in healthy controls, with the y-axis representing the percentage of I g D-M E B cells and the x-axis representing age. Panel F: Flow cytometry plots show the proportions of I g D-P C s and I g D-M E B cells in pediatric healthy controls and H I E S patients. Panel G: A scatter plot summarizes the proportions of I g D-M E B cells in pediatric healthy controls and H I E S patients, with the y-axis representing the percentage of I g D-M E B cells and the x-axis listing different patient groups. Panel H: A scatter plot summarizes the proportions of I g D-P C s in pediatric healthy controls and H I E S patients, with the y-axis representing the percentage of I g D-P C s and the x-axis listing different patient groups. Panel I: A heatmap shows the differential expression of m R N A s for modification slash glycosylation factors in tonsillar I g D-M E versus I g G slash I g A M E B cells, with genes discussed in the text highlighted in bold.
IgD responses involve complex glycosylation-regulated innate and adaptive BCR, CD40, TACI, and TLR signaling programs. (A–C) ELISA of serum IgD from adult or pediatric healthy controls (A-HCs and P-HCs, respectively), as well as PID or HIDS patients. 3, 7, 8, and 9, pooled PID cases corresponding to XLA, HIGM1, MyD88 deficiency, and LOCID from A; *, deleterious mutation; gray symbols, below the limit of detection; dotted line, saturation point. (D and E) Pearson’s correlation coefficient analysis of the relationship between age and frequency of tonsillar IgD-PCs (D) or IgD-ME B cells (E) (N = 22). (F–H) Representative flow cytometry (F) and summary graphs of IgD-ME B cell (G) and IgD-PC (H) proportions in P-HCs and HIES patients (N = 8). (I) Heatmap showing mRNAs for modification/glycosylation factors differentially expressed (adj. P <0.05 and |log2FC| >1) by tonsillar IgD-ME vs. IgG/IgA-ME B cells. Bold genes, discussed in the text. Data show results from one representative assay of at least three experiments summarized as mean ± SD (A–C, F), summarize multiple experiments (D, E, G, and H), or depict one experiment with multiple biological replicates (I). Significance was determined by the Kruskal–Wallis test followed by post hoc Dunn’s test (B). *P < 0.05.