Fig. 7: MYC-mTORC1 dysregulation is associated with follicular differentiation and impaired positive selection. | Nature Communications

Fig. 7: MYC-mTORC1 dysregulation is associated with follicular differentiation and impaired positive selection.

From: Defective germinal center selection results in persistence of self-reactive B cells from the primary to the secondary repertoire in Primary Antiphospholipid Syndrome

Fig. 7: MYC-mTORC1 dysregulation is associated with follicular differentiation and impaired positive selection.

A Circos plot depicting the IGHV:IGLV and IGHV:IGKV pairings for a HD and two representative PAPS patients. Pairing between IGHV3-11, 3-21, 3-74, 4-39, or 4-34 (pink segment), and IGKV (blue segment) or IGLV (green segment) gene are shown by the connecting lines inside the circle with thickness corresponding to pairing frequencies. B Frequencies of IGHV3-21, 3-74, 4-39 clonotypes in IGHM and IGHG/A isotypes in PAPS patients (n = 10) and HD (n = 7). C Violin plot representing normalized ADT level for B cell signaling and activation markers in IGHV4-39 clonotypes from APS patients (dark red), HD (dark blue), other clonotypes from PAPS patients (light red) and HD (light blue). D Dot plot for expression of mTORC1 and MYC selected genes among naive and memory cells according to clonotypes in PAPS patients and HD. E Dot plot for expression of pre-GC and plasmablast selected genes in naive cells according to clonotypes in PAPS patients and HD. F Violin plot representing pre-GC signature, SELL and CXCR5 gene expression according to clonotypes in patients and HD. G Frequency of plasmablast (CD38++CD27++) after B cell stimulation with CD40L + IL-21 + IL-4 for 6 days. Two-tailed Mann–Whitney test was used to compare groups. H Representative lineage trees for two clones in APS patients. I Representative amino acid VH alignment for IGHV4-39 clone (clone 1 depicted in H). J Frequency of positively charged amino acid induced by SHM in VH genes (top) of switched IgG/A B cells from HD (n = 8191) and PAPS patients (n = 9406). K Frequency of arginine residues induced by SHM in VH genes CDR of switched IgG/A B cells from HD (n = 7229) and PAPS patients (n = 6101). Data are presented as mean values ±SEM. Significance was determined using a Two-tailed Mann–Whitney test. ADT antibody-derived tag, CDR complementary determining region, HD healthy donor, MFI Mean fluorescence intensity, PAPS primary antiphospholipid syndrome, SHM somatic hypermutation.

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