Given the critical role of TFH cells in B-cell-mediated humoral immunity, investigations of the early fate commitment of TFH cells are very important, as the differentiation of TFH cells occurs within 48 h after acute viral infections.14,15 The transcriptional repressor B cell lymphoma-6 (Bcl-6) functions as a “master regulator” to govern early TFH cell differentiation.16–18 A rapid induction of Bcl-6 expression in de novo activated virus-specific CD4+ T cells represents a key step toward the TFH fate commitment. Here, CD4 is linked to viral infectious disease.