Chiodi and Scarlatti (163) have proposed that the B-cell dysfunctional profile (inhibition of both B-cell proliferation and antibody production) due to cellular exhaustion caused by HIV infection, could be explained by a specific pathway engaged via the expression of inhibitory receptors on the surface of TLM B-cells during HIV-1 infection, which includes the inhibitory receptor Fc receptor-like-4 [FCRL4, which is increased in B-cells during HIV-1 (164) infection, and acts by dampening B-cell receptor (BCR) signaling]. This evidence concerns the gene FCRL4 and HIV infectious disease.