title: Low frequency of plasma nerve-growth factor detection is associated with death of memory B lymphocytes in HIV-1 infection.
abstract: Nerve growth factor (NGF) regulates B cell activation and differentiation and is an autocrine survival factor for memory B lymphocytes. We have reported recently that the number of memory B cells is reduced during HIV-1 infection. In this study we evaluated whether alteration in the NGF supply was involved in memory B cell loss in HIV-1-infected subjects. High rate of cell death in vitro was observed in memory B cells from HIV-1-infected individuals compared to uninfected donors (26.2 +/- 2.5%versus 7.9 +/- 1.4%, P < 0.001). The increased expression of Fas on memory B cells from infected subjects did not enhance the susceptibility of the cells to Fas-mediated apoptosis in vitro. The frequency of NGF detection in plasma from HIV-1-infected subjects was significantly lower than in healthy donors (33.6%versus 63.6%, P < 0.001). Also, the median plasma NGF in HIV-1-infected individuals was significantly lower than in uninfected controls (5 versus 14 pg/ml, respectively, P < 0.01). Interestingly, the plasma NGF level was correlated directly 1 to the percentage of memory B cells (P < 0.05). HIV-1-infected subjects with a low number of peripheral memory B cells had a reduced incidence of plasmatic NGF (7.4%) compared to patients with a normal level of memory B cells (37%, P < 0.01). Moreover, the addition of recombinant NGF (1 micro g/ml) to cultures of purified B cells reduced cell death of memory B cells from HIV-1-infected subjects from 24.04 +/- 3.0% to 17.4 +/- 1.3% (P < 0.01). HIV-1-infected individuals also carried higher levels of natural anti-NGF autoantibodies compared to uninfected subjects. In conclusion, we found that memory B cells from HIV-1-infected individuals are primed for cell death. Our study suggests an association between low frequency of plasma NGF detection and the increased cell death of memory B lymphocytes observed during HIV-1 infection. Low levels of NGF in plasma may be due to reduced supply or to NGF binding to natural anti-NGF autoantibodies.
authors.affiliation: Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Titanji
authors.forename: A
authors.initials: A
authors.lastname: Nilsson
authors.forename: C
authors.initials: C
authors.lastname: Mörch
authors.forename: A
authors.initials: A
authors.lastname: Samuelsson
authors.forename: A
authors.initials: A
authors.lastname: Sönnerborg
authors.forename: S
authors.initials: S
authors.lastname: Grutzmeier
authors.forename: M
authors.initials: M
authors.lastname: Zazzi
authors.forename: A
authors.initials: A
authors.lastname: De Milito
mesh_terms: D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D016022:Case-Control Studies; D016923:Cell Death; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D015658:HIV Infections / Q000097:blood* / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008562:Membrane Glycoproteins / Q000032:analysis; D020932:Nerve Growth Factor / Q000097:blood* / Q000276:immunology; D018709:Statistics, Nonparametric; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis; D019014:fas Receptor / Q000032:analysis
chemical_list: D001323:Autoantibodies; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D019014:fas Receptor; D020932:Nerve Growth Factor