B cell activation in peripheral blood and lymph nodes during HIV infection.
BACKGROUND
The spontaneous in-vitro antibody synthesis observed in unstimulated lymphocyte cultures from HIV-infected patients closely reflects the in-vivo activation of the B cell compartment; however, the mechanisms underlying this phenomenon are far from clear.


METHODS
We compared the ability of peripheral blood mononuclear cells (PBMC) and lymph-node cells (LNC) from 10 HIV-infected patients to produce in vitro HIV-specific and total Ig spontaneously, and we correlated these parameters with tumour necrosis factor alpha (TNF-alpha) expression by CD4 T cells, viral dissemination in the organism, and the extent of HIV spread into lymph-node germinal centres, measured by in-situ hybridization (ISH).


RESULTS
In-vitro spontaneous synthesis of both HIV-specific and total antibody was significantly higher in PBMC than in LNC; the two variables showed a good correlation in LNC, but not in PBMC. In both compartments, no correlation was found between B cell activation and the percentage of CD4 T cells expressing TNF-alpha, which was increased compared with seronegative donors. Furthermore, no correlation was found between in-vitro spontaneous antibody synthesis and the number of T cells containing proviral HIV in PBMC and LNC, or the plasma levels of HIV RNA. On the contrary, a good correlation was found between HIV-specific B cell activation and the extent of viral spread into lymph-node germinal centres, evaluated by ISH.


CONCLUSIONS
These data suggest that the adhesion of HIV virions to the follicular dendritic cell network in lymph-node germinal centres may primarily contribute to sustaining the steady B cell activation observed in HIV-infected patients.
Zamarchi
Rita
R
Department of Oncology and Surgical Sciences, Interuniversity Center for Research on Cancer, University of Padova, Padua, Italy.
Barelli
Andrea
A
Borri
Alfredo
A
Petralia
Gaetano
G
Ometto
Lucia
L
Masiero
Sara
S
Chieco-Bianchi
Luigi
L
Amadori
Alberto
A
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D002448:Cell Adhesion; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D006678:HIV / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D015658:HIV Infections / Q000097:blood* / Q000276:immunology* / Q000821:virology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D017403:In Situ Hybridization; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation; D008297:Male; D012367:RNA, Viral / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007074:Immunoglobulin G; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha