Loss of memory (CD27) B lymphocytes in HIV-1 infection

Objectives: The mechanisms of B-cell dysfunction during HIV-1 infection, in cluding polyclonal B-cell activation, are poorly understood. We studied the phenotype and the functionality of peripheral memory B cells in HIV-1-infe cted subjects. Design: The phenotype of B cells and the responsiveness to T-cell dependent activation in vitro were analysed in 36 HIV-1-infected and 34 healthy subj ects. Methods: Phenotyping of B and T cells was performed by FAGS. IgG content wa s measured in plasma (by nephelometry) and cultures (by enzyme-linked immun osorbent assay) of B lymphocytes activated through CD40 or CD27 ligation. E xpression of Fas and Fas ligand was performed by FACS on B-cell subpopulati ons from five HIV-1-infected and four uninfected subjects. Results: The peripheral memory (CD27) B cells were significantly reduced in HIV-1-infected subjects. The amount of memory B cells was low in both drug -naive subjects and patients undergoing antiretroviral therapy. Ex vivo exp ression of CD70 (CD27 ligand) on T cells was significantly higher in HIV-1- nfected subjects and inversely correlated with the frequency of memory B ce lls. In spite of the reduced number of memory B cells, in vitro spontaneous and activation-induced IgG secretion was higher in HIV-1infected patients than in uninfected controls. The hyperactivation status of B lymphocytes in HIV-1-infected patients was further confirmed by the finding of upregulati on of Fas and FasL expression on memory B cells. Conclusions: Memory B lymphocytes are depleted from peripheral blood in HIV -1-infected subjects. Our ex vivo findings suggest that persistent T-cell a ctivation may contribute to loss of memory B cells through upregulation of Fas/FasL on these cells and terminal differentiation into plasma cells. (C) 2001 Lippincott Williams & Wilkins.