Primary HIV-1 infection sets the stage for important B lymphocyte dysfunctions.
OBJECTIVE
To investigate the effects of primary HIV-1 infection (PHI) and of two antiretroviral therapies [highly active antiretroviral therapy (HAART) or reverse transcriptase inhibitors (RTI)] on activation, differentiation and survival of B cells.


METHODS
Naive and memory B cells from three groups [PHI (31), chronic infection (26) and healthy donors (12)] were studied for surface expression of Fas, LAIR-1, CD70, intracellular expression of Bcl-2 and spontaneous apoptosis. Fluorescence activated cell sorting (IgD+IgM+CD19+CD27+) and short-term cell culture to analyse induction of CD25 on B cells were performed in five patients with PHI. Patients with PHI were sampled at baseline, and after 1 and 6 months of therapy. Results were analysed by parametric and non-parametric tests and by mathematical modelling.


RESULTS
In PHI, B cells were significantly decreased; naive and memory B lymphocytes showed a high degree of activation, manifested by hypergammaglobulinaemia, altered expression of Fas and LAIR-1, and high rate of spontaneous apoptosis. Antiretroviral treatment improved the activation/differentiation status of B cells, reduced apoptosis to levels comparable to those in healthy individuals and restored the ability of B cells to respond to T cell-dependent activation. B cells showed slightly better recovery in patients taking HAART than in those taking RTI. Decreased IgM-positive memory B cells and lower induction of CD25 expression on B cells upon T cell activation at diagnosis of PHI was shown in five patients tested. These parameters normalized after 6 months of therapy.


CONCLUSIONS
B cell dysfunctions found in chronic HIV-1 infection appear during PHI and initiation of antiretroviral therapy early during infection may help to preserve the B cell compartment.
Titanji
Kehmia
K
Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden.
Chiodi
Francesca
F
Bellocco
Rino
R
Schepis
Danika
D
Osorio
Lyda
L
Tassandin
Chiara
C
Tambussi
Giuseppe
G
Grutzmeier
Sven
S
Lopalco
Lucia
L
De Milito
Angelo
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D019254:Genes, bcl-2 / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D006942:Hypergammaglobulinemia / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011971:Receptors, Immunologic / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D019014:fas Receptor
D015703:Antigens, CD; C491901:FAS protein, human; D011971:Receptors, Immunologic; D018124:Receptors, Tumor Necrosis Factor; D018894:Reverse Transcriptase Inhibitors; D019014:fas Receptor; C108073:leukocyte-associated immunoglobulin-like receptor 1