Figure 1. TACI triggers CSR by cooperating with TLR ligands.
(a) Immunofluorescence staining of tonsil (top) and splenic (bottom) tissues for IgD (green), TACI (red), and nuclei (blue). Dashed line, follicle; EP, epithelium; FM, follicular mantle; FO, follicle; GC, germinal center; MZ; marginal zone; SE, sub-epithelium; RP, red pulp. Original magnification, ×10 (left panels) or ×63 (right panels). (b–e) QRT-PCR of Iγ1-Cγ1, Iγ1-Cμ and AICDA in naïve (b–d) or lymphoblastoid (e) B cells from healthy donors (HD) or CVID patients with various heterozygous TACI substitutions cultured for 2 or 4 days with or without anti-TACI, IL-10 and/or IL-4. Results are normalized to ACTB (encoding β-actin) mRNA; RE, relative expression compared to B cells incubated with a control antibody (ctrl). (f) Flow cytometry of TACI on primary CD19+CD27+ B cells from a HD or CVID patient with homozygous S144X/S144X TACI substitution. Red histograms, ctrl; blue histograms, anti-TACI. (g) AICDA and Iγ1-Cμ in primary naive B cells from CVID case shown in f incubated with BAFF or APRIL plus IL-4 for 6 d. (h) Flow cytometry of IgG, IgA and CD27 on primary naive B cells incubated for 7 days with ctr, anti-TACI, IL-10 and/or CpG DNA. Numbers indicate percentages. (i) Flow cytometry of IgG and IgA (upper panels) and ELISA of secreted IgG and IgA (bottom panels) from B cells stimulated as in h. *P < 0.05 (one-tailed unpaired Student’s t-test). Data are from one of three experiments with similar results (a–h) or summarize three experiments (i; error bars, s.d.).