Detection of peripheral HIV-1-specific memory B cells in patients untreated or receiving highly active antiretroviral therapy.
OBJECTIVE
To examine whether polyclonal activation of circulating B cells, in a process that involves CD40-CD40 ligand and cytokine interactions, could induced HIV-1-specific memory B cells to synthesize HIV-1-specific antibodies.


METHODS
B cells from 26 HIV-1-infected patients were cultured with a CD40L-transfected cell line plus interleukins 2 and 10 and tested for their secretion of HIV-1- and Toxoplasma gondii-specific antibodies.


RESULTS
In vitro activated B lymphocytes from HIV-1-infected patients secreted anti-HIV-1-specific antibodies. B cells from HIV-1-infected patients as well as those from controls chronically infected by T. gondii synthesized T. gondii-specific antibodies. HIV-1-specific IgG-, IgA- or IgM-secreting B cells represented approximately 1 x 10(-4) to 1 x 10(-5) of total circulating B cells and 1 x 10(-2) to 1 x 10(-3) of immunoglobulin-secreting cells. HIV-1-specific memory B cells were found in 9/9 untreated patients and in 8/17 patients receiving highly active antiretroviral therapy (HAART). The other nine patients showed a normal CD40-CD40L B cell response and six of them produced T. gondii-specific antibody B cells. The follow-up of seven patients indicated that HIV-1-specific memory B cells became undetectable after 8 to 46 months of HAART, whereas T. gondii-specific memory B cells persisted in parasite coinfected patients.


CONCLUSIONS
Circulating memory HIV-1-specific B cells were detected in untreated patients and in about half of the patients taking HAART, suggesting that persistent low-level ongoing viral replication is not sufficient to maintain HIV-1-specific memory B cells.
Fondere
Jean-Michel
JM
Virology Laboratory, Hospital Lapeyronie, INSERM U470, Bâtiment Crastes de Paulet, Hospital A. Villeneuve, France.
Huguet
Marie-France
MF
Yssel
Hans
H
Baillat
Vincent
V
Reynes
Jacques
J
van de Perre
Philippe
P
Vendrell
Jean-Pierre
JP
D019380:Anti-HIV Agents / Q000627:therapeutic use; D000918:Antibody Specificity; D023241:Antiretroviral Therapy, Highly Active; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology; D002478:Cells, Cultured; D002908:Chronic Disease; D015483:HIV Antibodies / Q000096:biosynthesis; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication
D019380:Anti-HIV Agents; D015483:HIV Antibodies; D023201:CD40 Ligand