Indeed, B-cell specific TRAF3 KO mice have severely expanded B-cell compartments with splenomegaly and lymphadenopathy, due to abnormal basal level of non-canonical NF-κB activity, suggesting a B-cell intrinsic function in lymphoid organ development.314–317 Additionally, non-canonical NF-κB directly affects B-cell survival. Here, NFKB1 is linked to Splenomegaly.