Lymphokine production by B cells from normal and HIV-infected individuals.
Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are both secreted by in vivo-activated normal B cells and by in vivo-activated B cells from patients with polyclonal B-cell activation, including individuals infected with the human immunodeficiency virus (HIV). Furthermore, IL-6 and TNF-alpha are involved in autocrine and paracrine regulation of human B-cell differentiation. Following in vitro stimulation of normal B cells with Staphylococcus aureus Cowan strain I and IL-2, there is a rapid but brief increase in supernatant levels of TNF-alpha. There is also an initial increase followed by a subsequent and more sustained increase in IL-6 production. The secondary rise in IL-6 production is dependent upon the prior production of TNF-alpha. There is no significant difference in IL-6 and TNF-alpha secretion by CD5 positive versus CD5 negative tonsillar B cells. Ig production by normal in vitro-activated B cells and freshly isolated B cells from patients with hypergammaglobulinemia is largely dependent upon TNF-alpha and IL-6 production. As another measure of B-cell TNF-alpha and IL-6 production, freshly isolated B cells from HIV-infected individuals induce virus production by chronically HIV-infected cells in which HIV production is known to be triggered by a variety of cytokines. By contrast, freshly isolated B cells from normal controls fail to increase HIV production unless they are stimulated in vitro. Thus, the spontaneous production of IL-6 and TNF-alpha by B cells from individuals infected with HIV may contribute to viral expression as well as to the hypergammaglobulinemia often associated with HIV infection.
Kehrl
J H
JH
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Rieckmann
P
P
Kozlow
E
E
Fauci
A S
AS
D015703:Antigens, CD / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens; D016207:Cytokines / Q000235:genetics*; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics; D019947:Receptors, Interleukin-6; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D015703:Antigens, CD; D018956:CD5 Antigens; D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha