Human immunoglobulin selection associated with class switch and possible tolerogenic origins for Cδ class-switched B cells
J. Clin. Invest. Nai-Ying Zheng, et al. 113:1188 doi:10.1172/JCI20255 [Go to this article.]

Figure 2
V_H4-34⁺ B cell selection correlates with antibody isotype and is due to iI antigen autoreactivity. V_H4 family genes were randomly cloned and sequenced from various B cell subpopulations sorted by flow cytometry. B cell subpopulation phenotypes are in the text, and Table 1 lists populations isolated from each donor and number of V genes sequenced per population. (A) V_H4-34 usage in the various subpopulations of two donors. Similar analyses of all 29 donors are presented in Supplemental Figure 1. (B) Average use of V_H4-34 by the various B cell subpopulations between donors (means ± SD; Table 2 lists mean use of the remaining V_H4 genes). V_H4-34 encodes antibodies from the various IgM populations significantly more than the IgG populations (Student’s t test, P < 0.05) and was used in the Cδ-CS populations more than all others (P < 0.01). (C) V_H4-34 usage organized by Ig class. Student’s t test probabilities are indicated. *P < 0.0001; **P = 0.004; ^#P = 0.002; ^##P = 0.0008. (D) V_H4-34 is probably selected due to its autoreactivity to iI glycans. Bars indicate mean ± SD of V genes with mutations at amino acid positions 7, 23, 24, or 25. These amino acids are used for iI glycan binding by V_H4-34⁺ antibodies (W7 and AVY23–25). Despite equivalent mutation frequencies between V_H4-34⁺ and other V_H4 genes (Table 3), mutations at these amino acid positions are significantly selected only for V_H4-34 genes, and only in association with CSR (χ² probabilities are indicated). ^†P < 0.05.