Figure 4. Bcl-6 drives CXCR5 expression via repression of Id2-E2A pathway.

a, Gene expression of Id2 from RNA-seq data of LCMV_Arm infected mice or KLH-gp₆₁ immunized mice. Each data point was collected from three (LCMV_Arm) or four (KLH-gp₆₁) independent experiments.

b, GSEA of E2A bound genes from thymocytes^22,55 in comparison to Cluster 4 genes between Bcl6^f/fPrdm1^f/f T_FH-like cells and Prdm1^f/f T_FH cells.

c, A hypothetical model of Bcl-6 regulation of T_FH genes primarily via inhibition of Id2 and Prdm1/Blimp-1.

d, Schematic of the SMARTA cell transfer system used for KLH-gp₆₁ immunization. Wild-type, Bcl6^f/fPrdm1^f/f, or Bcl6^f/fPrdm1^f/fId2^f/f Cre^CD4 SMARTA CD4⁺ T were transferred to C57BL/6 host mice, followed by immunization of the host mice with KLH-gp₆₁ in alum + cGAMP, and analyzed 8 days later. See Fig. 4e,f and Extended Data Fig.4a.

e,f, Representative flow cytometry of CXCR5^hi T_FH, CXCR5^hiPD-1^hi and CXCR5^hiPSGL1^lo GC-T_FH SMARTA cell subsets from dLNs of KLH-gp₆₁ immunized mice in Fig.4d. Two independent experiments were performed; each dot represents one mouse (n = 4). Data are mean ± s.d., unpaired two-tailed Student’s t-test.

g, Quantification of CXCR5^hiSLAM^lo T_FH and CXCR5^hiPSGL1^lo GC-T_FH cells, gated on SMARTA cells from spleens of LCMV_Arm infected mice. Two independent experiments were performed; each dot represents one mouse (n = 4). Data are mean ± s.d., unpaired two-tailed Student’s t-test. See Extended Data Fig.4b–g.