B cell activation during HIV-1 infection. II. Cell-to-cell interactions and cytokine requirement.
This study examined the mechanisms underlying the intense activation of HIV-1-specific B cells observed in peripheral blood of HIV-1-infected subjects. Spontaneous in vitro synthesis of anti-HIV-1 antibodies, as well as total Ig production, were dramatically reduced by accessory cell, but not T cell removal. This fall was counteracted by addition of rIL-6, but not other cytokines, to monocyte-depleted cultures; moreover, antisera against IL-6 suppressed spontaneous anti-HIV-1 antibody synthesis in a dose-dependent manner. Although IL-6 apparently sustained HIV-1-specific B cell activation, no increase in serum IL-6 levels was observed; PBMC from seropositive subjects did not produce increased amounts of IL-6 in vitro, compared to seronegative controls, both spontaneously and in the presence of LPS stimulation; finally, no constitutive expression of IL-6 gene could be documented in freshly isolated PBMC. These findings indicate that IL-6 may play a central role in HIV-1-specific B cell activation in seropositive patients, and further stress the importance of this cytokine during HIV-1 infection.
Amadori
A
A
Institute of Oncology, University of Padua, Italy.
Zamarchi
R
R
Veronese
M L
ML
Panozzo
M
M
Barelli
A
A
Borri
A
A
Sironi
M
M
Colotta
F
F
Mantovani
A
A
Chieco-Bianchi
L
L
D001402:B-Lymphocytes / Q000276:immunology*; D015152:Blotting, Northern; D002450:Cell Communication; D016207:Cytokines / Q000502:physiology*; D015870:Gene Expression; D006678:HIV / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000235:genetics
D016207:Cytokines; D015483:HIV Antibodies; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D012333:RNA, Messenger; D015847:Interleukin-4