HIV glycoprotein gp120, found on the surface of the virus, inactivates human antibody-producing B immune cells, according to a report published this week in Nature Immunology. These findings explain why HIV patients have poor antibody responses.

HIV is known to cause a progressive loss of CD4+ “helper” T immune cells, leading to diminished immune system function and susceptibility to other opportunistic infections. Why robust antibody responses are not generated early in infection, when T cell numbers are still relatively normal, has remained a mystery.

Claudia Cicala and colleagues show that HIV gp120 also directly acts on B cells via the host cell’s surface receptor alpha4-beta7. Signaling through alpha4?beta7 on B cells induces expression of an immunosuppressive molecule and an inhibitory receptor. This gp120-induced response profoundly disables B cells and reduces their ability to produce neutralizing antibodies against the virus.