Abstract
WHEREAS immunocompetent precursor B cells recognise antigenic determinants by way of specific surface receptors (an interaction which presumably initiates cell division1,2), the binding of antigen to surface receptors alone does not result in the differentiation of B cells to antibody-secreting cells. To accomplish this differentiation step a second signal is needed. This signal may be provided by T cells in the form of a soluble factor which they produce in vitro after contact with antigen3–5. Besides T cells, activated peritoneal macrophages have also been shown to produce a factor which allows B cells from athymic Nu/Nu mice to produce antibody against fowl gammaglobulin in vitro. Production of this factor is increased by addition of bacterial lipopolysaccharide (LPS) to the culture medium6. LPS itself has been shown to provide the second signal (antigen being the first) for antibody production by B cells7, but it is not clear whether the effect on antigen-reactive B cells is direct, or mediated by other cells. We report here that injection of LPS, in certain conditions in the mouse, induces the release of factors into the serum which enable B cells to produce antibody to heterologous red-cell antigen, in vitro in the absence of helper T cells. The factor is released in large quantity when LPS is injected into mice that have been primed with BCG. It is hardly, if at all, detectable in the serum of mice injected with LPS but not pretreated with BCG. Our investigation was prompted by the discovery that serum from BCG-infected mice given LPS causes acute necrosis of established tumour grafts in syngeneic mice (tumour necrosis serum, TNS)8. After partial purification, tumour-necrotising activity was shown to reside in a glycoprotein fraction (termed tumour necrosis factor, TNF) with a molecular weight of about 150,000 that migrates with the α-2-globulins9.
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HOFFMANN, M., GREEN, S., OLD, L. et al. Serum containing endotoxin-induced tumour necrosis factor substitutes for helper T cells. Nature 263, 416–417 (1976). https://doi.org/10.1038/263416a0
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DOI: https://doi.org/10.1038/263416a0
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