HIV-1 infection of CD4 T cells impairs antigen-specific B cell function

Failures to produce neutralizing antibodies upon HIV-1 infection result in part from B cell dysfunction due to unspecific B cell activation. How HIV-1 affects antigen-specific B cell functions remains elusive. Using an adoptive transfer mouse model and ex vivo HIV infection of human tonsil tissue we found that expression of the HIV-1 pathogenesis factor NEF in CD4 T cells undermines their helper function and impairs cognate B cell functions including mounting of efficient specific IgG responses. NEF interfered with T cell help via a specific protein interaction motif that prevents polarized cytokine secretion at the T cell - B cell immune synapse. This interference reduced B cell activation and proliferation and thus disrupted germinal center formation and affinity maturation. These results identify NEF as a key component for HIV-mediated dysfunction of antigen-specific B cells. Therapeutic targeting of the identified molecular surface in NEF will facilitate host control of HIV infection. We used microarray analysis to understand 15 samples, naïve B cells, B cells cocultured with control T cells for 4hrs and 24hrs, B cells cocultured with (Nef-WT or Nef-mutant expressing) T cells for 4hrs and 24hrs