B cells in HIV pathogenesis

The induction of a virus-clearing humoral immune response in natural HIV infection is impaired. Insights into early events in HIV infection that affect B-cell responses and antibody development are addressed and related to strategies for the design of an HIV vaccine.

Broadly neutralizing antibody responses do not develop early in HIV-1 infection, and recent reports highlight the role of preexisting suboptimal B-cell populations that can dominate the early antibody response. Furthermore, from the earliest phases of infection, virus replication is a driving force behind alterations in the B cell and T-follicular helper cell (TFH) compartments. Paradoxically, the factors that drive these abnormalities, such as high virus load, duration of infection, and increased viral diversity, are likely necessary for the development of both TFH and broadly neutralizing antibodies.

These data provide new insights into prerequisites for an effective HIV vaccine. First, a vaccine should induce specific B-cell lineages so that preexisting cross-reactivity is avoided and, additionally, it must mimic high levels of diverse antigen in the absence of chronic virus replication within immune cells to activate high levels of quality of TFH and stimulate antibody maturation.