A VH clonal deficit in human immunodeficiency virus-positive individuals reflects a B-cell maturational arrest.
A major feature of human immunodeficiency virus (HIV) infection is disordered B-cell function, which paradoxically includes both pathologic overactivity (elevated serum antibodies, lymphadenopathy, and increased risk for lymphoma) and underactivity (impaired antibody immunity, particularly to bacterial polysaccharide antigens). B-cell immune dysfunction contributes significantly to HIV-related morbidity and also represents an obstacle to eventual definitive treatment by anti-HIV immunization. Our laboratory has recently identified in normal B-cell populations certain VH gene subfamilies with a developmentally regulated pattern of utilization. In particular, B cells bearing rearranged VH3L were rare in the germinal center but uniformly abundant in the blood and lymphoid mantle zone. We used this index gene subfamily as a clonal criterion for the pattern of B-cell development in lymphocytes of HIV-positive individuals. In a series of 19 HIV-positive subjects, a striking deficit of VH3L B cells was observed; in contrast, none of the 16 normal subjects showed this abnormality. Other VH subfamilies (VH1N, VH4/6, and VH5N) were unaffected in the HIV-positive patients. This VH3L clonal deficit and other recent phenotype and histopathologic findings suggest that the general B-cell dysfunction in HIV is due to a discreet maturational arrest at the germinal center stage.
Berberian
L
L
Department of Pathology, UCLA School of Medicine 90024-1732.
Valles-Ayoub
Y
Y
Sun
N
N
Martinez-Maza
O
O
Braun
J
J
D001402:B-Lymphocytes / Q000737:chemistry / Q000473:pathology*; D001483:Base Sequence; D002454:Cell Differentiation; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D015321:Gene Rearrangement / Q000235:genetics; D005814:Genes, Viral / Q000235:genetics*; D006679:HIV Seropositivity / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008198:Lymph Nodes / Q000737:chemistry / Q000473:pathology; D008214:Lymphocytes / Q000737:chemistry / Q000473:pathology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction
D004279:DNA, Viral