Memory B-cell depletion is a feature of HIV-2 infection even in the absence of detectable viremia.
OBJECTIVE
Memory B-cell loss has long been recognized as an important contributor to HIV immunodeficiency. HIV-2 infection, which is characterized by a slow rate of progression to AIDS and reduced to undetectable viremia, provides a unique model to investigate B-cell disturbances.


METHODS
B-cell subsets were evaluated in 38 HIV-2-infected individuals, along with markers of T-cell activation and serum levels of immunoglobulins and a major B-cell homeostatic cytokine, B-cell activating factor (BAFF). Untreated HIV-1-infected and seronegative control individuals were studied in parallel. Statistical analysis was performed using Mann-Whitney tests and Spearman's correlations.


RESULTS
We found that HIV-2 was associated with significant depletion of both unswitched (CD27(+)IgD(+)) and switched (CD27(+)IgD(neg)) memory B-cells that directly correlated with T-cell activation, even in individuals with undetectable plasma viral load. Nevertheless, the presence of detectable viremia, even at low levels, was associated with significant memory B-cell loss and higher BAFF levels. Moreover, these alterations were not recovered by antiretroviral-therapy, as treated HIV-2-infected patients showed more pronounced B-cell disturbances, possibly related to their extended length of infection.


CONCLUSIONS
These first data regarding B-cell imbalances during HIV-2 infection show that, irrespective of viremia, prolonged HIV infection leads to irreversible damage of memory B-cell homeostasis.
Unidade de Imunologia Clínica, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
Rita
R
Tendeiro
Sofia
S
Fernandes
Russell B
RB
Foxall
José M
JM
Marcelino
Nuno
N
Taveira
Rui S
RS
Soares
António P
AP
Baptista
Rita
R
Cavaleiro
Perpétua
P
Gomes
Rui M M
RM
Victorino
Ana E
AE
Sousa
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology; D053264:B-Cell Activating Factor / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D018023:HIV Seronegativity / Q000276:immunology; D006679:HIV Seropositivity / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D015498:HIV-2 / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load; D014766:Viremia / Q000175:diagnosis / Q000821:virology
D019380:Anti-HIV Agents; D053264:B-Cell Activating Factor; D012367:RNA, Viral