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Impairment of B-lymphocyte differentiation induced by dual triggering of the B-cell antigen receptor and CD40 in advanced HIV-1-disease.
Conge AM; Tarte K; Reynes J; Segondy M; Gerfaux J; Zembala M; Vendrell
January 30, 1999
AIDS. 1998 Aug 20;12(12):1437-49. Unique Identifier : AIDSLINE

OBJECTIVE: This study was performed to investigate the hyporeactivity of purified B lymphocytes from HIV-1-infected patients. DESIGN: 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. CONCLUSION: 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.

JOURNAL ARTICLE Adult Antibodies, Monoclonal Antigens, CD40/*IMMUNOLOGY Apoptosis B-Lymphocytes/*IMMUNOLOGY Cell Cycle Cell Differentiation Enzyme-Linked Immunosorbent Assay Female Human HIV Antibodies/BLOOD HIV Infections/*IMMUNOLOGY *HIV-1 IgG/BLOOD Immunomagnetic Separation Lymphocyte Transformation Male Middle Age Receptors, Antigen, B-Cell/*IMMUNOLOGY Support, Non-U.S. Gov't Viral Load