Fig. 1: γ3-α inversion activates predominantly deletional Sγ3 CSR and orientation-unbiased Sα CSR within the Igh domain.

a Schematic of the Igh locus from V(D)J exon to 3′CBEs in CH12F3PO cells and an illustration of the generation of γ3-αInv cells. b Illustration of deletional and inversional joining between the donor Sμ and an acceptor Sx in CSR. The CSR joining features were measured by CSR-HTGTS-seq with 5′Sμ bait. c CSR-HTGTS-seq analysis of break joining between 5′Sμ and acceptor S regions in CH12F3PO and γ3-αInv cells stimulated with αCD40/IL4/TGFβ for 72 h. Junctions within the Igh constant region are plotted at a 2.25 kb bin size. Data are presented as mean ± s.e.m. from three independent experiments. d Joining features of Sμ–Sα junctions in CH12F3PO and γ3-αInv cells. Data are presented as mean ± s.e.m. from three independent experiments. e Bar graph shows the inversional joining of Sμ–Sα junctions in CH12F3PO and γ3-αInv cells. Data are presented as mean ± s.e.m. from six independent &experiments. P-values were calculated via an unpaired two-tailed Student’s t-test. f Pro-seq and 3C-HTGTS with iEμ/Iμ or 3′RR bait (blue asterisks) show the transcription status and chromatin interaction of the Igh locus from CH12F3PO cells. g Pro-seq and 3C-HTGTS with iEμ/Iμ or 3′RR bait (blue asterisks) show the transcription status and chromatin interaction of the Igh locus from γ3-αInv cells. h Bar graph shows the relative transcription activity of the Cγ3 unit and the Cα unit in CH12F3PO and γ3-αInv cells. Data are presented as mean ± s.e.m. from three independent experiments. P-values were calculated via a paired two-tailed Student’s t-test. i Bar graph shows the relative interaction frequency between iEμ/Iμ bait with Cγ3 unit and Cα unit in CH12F3PO and γ3-αInv cells. Data are presented as mean ± s.e.m. from three independent experiments. P-values were calculated via a paired two-tailed Student’s t-test. Source data are provided as a Source Data file.