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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.

journal_name

Clin Exp Immunol

journal_title

Clinical and experimental immunology

authors

Titanji K,Nilsson A,Mörch C,Samuelsson A,Sönnerborg A,Grutzmeier S,Zazzi M,De Milito A

doi

10.1046/j.1365-2249.2003.02145.x

subject

Has Abstract

pub_date

2003-05-01 00:00:00

pages

297-303

issue

eissn

0009-9104

issn

1365-2249

pii

2145

journal_volume

132

pub_type

杂志文章

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Low frequency of plasma nerve-growth factor detection is associated with death of memory B lymphocytes in HIV-1 infection.