HIV induces IL-6 production by human B lymphocytes. Role of IL-4.
In vitro, normal B cells can produce TNF-alpha and IL-6 when activated with a first signal, and cytokines and B lymphocytes from some HIV-infected individuals spontaneously secrete TNF-alpha and IL-6, although the direct involvement of HIV has not been fully explored. In this study, we examined the effects of HIV (purified virus and a recombinant envelope protein) and various IL on TNF-alpha and IL-6 in vitro production by highly purified normal B cells. HIV alone did not induce IL-6 or TNF-alpha production by B cells from healthy subjects. HIV induced IL-6 production (500 to 1500 pg) in the presence of IL-4, with a slight production of TNF-alpha. IL-6 production occurred independently of the presence or absence of TNF-alpha in contrast with Staphylococcus aureus cowan + IL-2-activated B cells. Other IL, particularly IL-2, were unable to induce IL-6 secretion by HIV-activated B cells. In vivo-activated B cells from HIV-infected patients spontaneously produce moderate quantities of IL-6 and TNF-alpha. This secretion was markedly increased by HIV, suggesting that IL-6-secreting B cells contain anti-HIV antibody-producing B cells. However, contrary to normal B cells, IL-6 production by B cells from HIV-infected patients was not further enhanced by IL-4. Then HIV itself is able to induce an autocrine production of IL-6 upon interaction with IL-4, which can contribute to the hypergammaglobulinemia and to the global B cell dysfunction observed in HIV-infected patients.
Boue
F
F
INSERM, U131 Hôpital Antoine Béclère, Clamart, France.
Wallon
C
C
Goujard
C
C
Barre-Sinoussi
F
F
Galanaud
P
P
Delfraissy
J F
JF
D015703:Antigens, CD / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D018956:CD5 Antigens; D015686:Gene Products, env / Q000276:immunology*; D006678:HIV / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D019302:HIV Envelope Protein gp160; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D015847:Interleukin-4 / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D011498:Protein Precursors / Q000276:immunology*; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015703:Antigens, CD; D018956:CD5 Antigens; D015686:Gene Products, env; D015488:HIV Antigens; D019302:HIV Envelope Protein gp160; D015850:Interleukin-6; D011498:Protein Precursors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4