As such, given the facts that HIV-Transgenic and BAFF-Transgenic mice presented a breakage of tolerance and autoimmunity [8,28,29,30], and that excess BAFF and MZ B-cell dysregulations have also been reported in the context of autoimmune diseases such as Systemic Lupus Erythematosus (SLE) and Sjögren Syndrome (SS) [31], it would be sound to bear in mind that MZ B-cell antibody responses in the context of excess BAFF may be nourishing polyclonal, possibly auto-reactive, low-affinity antibody responses, whose pertinence in the battle against HIV have yet to be determined. This evidence concerns the gene TNFSF13B and autoimmune disease.