A VH clonal deficit in human immunodeficiency virus-positive individuals reflects a B-cell maturational arrest. Blood

A major feature of human immunodeficiency virus (HIV) infection is disordered B-cell function, which paradoxically includes both pathologic overactivity (elevated serum anti-bodies, lymphadenopathy, and increased risk for lymphoma) and underactivity (impaired antibody immunity, particularly to bacterial polysaccharide antigens). B-cell immune dysfunc-tion contributes significantly to HIV-related morbidity and also represents an obstacle to eventual definitive treatment by anti-HIV immunization. Our laboratory has recently identi-fied in normal B-cell populations certain VH gene subfamilies with a developmentally regulated pattern of utilization. In particular, B cells bearing rearranged VHBL were rare in the germinal center but uniformly abundant in the blood and N NORMAL individuals a critical step in memory B-cell I differentiation occurs in the germinal center, a special-ized lymphoid microenvironment transiently inhabited b