Impairment of B-lymphocyte differentiation induced by dual triggering of the B-cell antigen receptor and CD40 in advanced HIV-1-disease.
OBJECTIVE
This study was performed to investigate the hyporeactivity of purified B lymphocytes from HIV-1-infected patients.


METHODS
Given the importance of the B-cell Ag receptor (BCR) and CD40 in B-lymphocyte activation, we assessed the capacity of purified peripheral blood B lymphocytes from HIV-1-infected patients to differentiate into Ig-secreting cells in a T-cell- and accessory-cell-independent system of BCR and CD40 costimulation.


METHODS
B lymphocytes from 21 HIV-1-infected patients were purified by immunomagnetic cell separation and costimulated with immobilized anti-CD40 monoclonal antibodies and Staphylococcus aureus Cowan I particles in the presence of interleukin (IL)-2 and IL-10. Homotypic aggregate formation, apoptosis, cell cycle entrance, proliferation and Ig secretion of B cells were analysed.


RESULTS
Costimulation by the BCR and CD40 induced proliferation and differentiation of B lymphocytes into Ig-secreting cells in 13 patients (group I) but not in eight patients (group II). For three patients in group II, the dual triggering induced apoptosis of B cells. The unexpected inability of these cells to differentiate was associated with a high CD38 expression and a weak spontaneous production of Ig or anti-HIV-1 antibodies in patients with a high viral load and a low CD4+ lymphocyte count. Despite this anomaly, the B cells from group II were able to progress through the cell cycle after stimulation with a combination of phorbol ester and ionomycin in complete medium, suggesting an impairment in BCR and CD40 early signal transduction.


CONCLUSIONS
Intrinsic in vitro hyporeactivity of B lymphocytes to dual triggering of BCR and CD40 was observed in advanced HIV-1 disease and appeared to be related to in vivo hyperactivation of B cells.
Conge
A M
AM
Centre National Recherche Scientifique, Laboratoire d'Immunologie des Infections Retrovirales, Institut de Biologie, Montpellier, France.
Tarte
K
K
Reynes
J
J
Segondy
M
M
Gerfaux
J
J
Zembala
M
M
Vendrell
J P
JP
D000328:Adult; D000911:Antibodies, Monoclonal; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D002453:Cell Cycle; D002454:Cell Differentiation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D018189:Immunomagnetic Separation; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D019562:Viral Load
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D015483:HIV Antibodies; D007074:Immunoglobulin G; D011947:Receptors, Antigen, B-Cell