Chronic low-level BCR cross-linkage and a lack of sufficient costimulation are believed to result in B-cell anergy, whereas high BCR cross-linkage with costimulation leads to activation or without proper costimulation leads to clonal deletion. B cells of several types in humans have been demonstrated to be autoreactive and anergic (top). In addition, memory B cells (bottom) from patients with HIV have been shown to be “exhausted,” which is similar to anergy. B cells with a similar phenotype have also been found in other chronic infectious diseases including HCV8 and malaria.7
