Specific antibody production by blood B cells is retained in late stage drug-naïve HIV-infected Africans.
Unseparated peripheral blood mononuclear cells (PBMCs) obtained from drug-naïve African individuals living in a context of multi-infections and presenting with high viral load (VL), were cultured in vitro and tested for their ability to produce antibodies (Abs) reacting with HIV-1 antigens. Within these PBMCs, circulating B cells were differentiated in vitro and produced IgG Abs against not only ENV, but also GAG and POL proteins. Under similar experimental conditions, HAART treated patients produced Abs to ENV proteins only. The in vitro antibody production by drug-naïve individuals' PBMCs depended on exogenous cytokines (IL-2 and IL-10) but neither on the re-stimulation of reactive cells in cultures by purified HIV-1-gp160 antigen nor on the re-engagement of CD40 surface molecules. Further, it was not abrogated by the addition of various monoclonal Abs (mAbs) to co-stimulatory molecules. This suggests that the in vitro antibody production by drug-naïve individuals' PBMCs resulted from the maturation of already envelope and core antigen-primed, differentiated B cells, presumably pre-plasma cells, which are not known to circulate at homeostasy. As in vitro produced Abs retained the capacity of binding antigen and forming complexes, this study provides pre-clinical support for functional humoral responses despite major HIV- and other tropical pathogen-induced B cell perturbations.
Béniguel
Lydie
L
GIMAP EA3064, Faculté de Médecine, Université J. Monnet, St-Etienne, France.
Bégaud
Evelyne
E
Cognasse
Fabrice
F
Gabrié
Philippe
P
Mbolidi
Christophe D
CD
Marovich
Mary A
MA
Cazorla
Céline
C
Lucht
Frédéric
F
Genin
Christian
C
Garraud
Olivier
O
D000293:Adolescent; D000328:Adult; D000349:Africa / Q000208:ethnology; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology*; D044383:Black People; D001782:Blood Donors; D002478:Cells, Cultured; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis / Q000097:blood* / Q000276:immunology*; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged
D019380:Anti-HIV Agents; D015483:HIV Antibodies; D015488:HIV Antigens; D019302:HIV Envelope Protein gp160