ICOS is required for providing costimulatory signals for optimal Tfh and GC B-cell differentiation44, 45, 46, 47 and for persistent directional motility and follicular recruitment of activated CD4+ T cells48 and failed Icos mRNA repression is associated with accumulation of Tfh cells in lupus-prone Roquin-1/2 mutant mice6, 19, 49. Here, CD4 is linked to systemic lupus erythematosus.