Myeloid-specific Znrf1 deletion caused age-dependent spontaneous splenomegaly and, upon allosensitization, elevated CD4<sup>+</sup>/CD8<sup>+</sup> T-cell ratios, enlarged germinal centers with heightened IL-21/Tfh activity, and augmented alloantibody production. This evidence concerns the gene CD4 and Splenomegaly.