HIV-1 induces phenotypic and functional perturbations of B cells in chronically infected individuals.
A number of perturbations of B cells has been described in the setting of HIV infection; however, most remain poorly understood. To directly address the effect of HIV replication on B cell function, we investigated the capacity of B cells isolated from HIV-infected patients to respond to a variety of stimuli before and after reduction of viremia by effective antiretroviral therapy. B cells taken from patients with high levels of plasma viremia were defective in their proliferative responses to various stimuli. Viremia was also associated with the appearance of a subpopulation of B cells that expressed reduced levels of CD21. After fractionation into CD21(high)- and CD21(low)-expressing B cells, the CD21(low) fraction showed dramatically reduced proliferation in response to B cell stimuli and enhanced secretion of immunoglobulins when compared with the CD21(high) fraction. Electron microscopic analysis of each fraction revealed cells with plasmacytoid features in the CD21(low) B cell population but not in the CD21(high) fraction. These results indicate that HIV viremia induces the appearance of a subset of B cells whose function is impaired and which may be responsible for the hypergammaglobulinemia associated with HIV disease.
Moir
S
S
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, and Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. smoir@niaid.nih.gov
Malaspina
A
A
Ogwaro
K M
KM
Donoghue
E T
ET
Hallahan
C W
CW
Ehler
L A
LA
Liu
S
S
Adelsberger
J
J
Lapointe
R
R
Hwu
P
P
Baseler
M
M
Orenstein
J M
JM
Chun
T W
TW
Mican
J A
JA
Fauci
A S
AS
D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000648:ultrastructure; D001402:B-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D006942:Hypergammaglobulinemia / Q000209:etiology; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008854:Microscopy, Electron; D017464:Receptors, Complement 3d / Q000235:genetics / Q000378:metabolism; D014766:Viremia / Q000235:genetics / Q000276:immunology
D018941:Antigens, CD19; D017931:DNA Primers; D017464:Receptors, Complement 3d