Cliff, Jacqueline M.; (2000) The role of autocrine factors in B cell activation. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The activation of B cells following encounter with antigen is tightly regulated during the course of a humoral immune response. The roles of factors produced by accessory cells, particularly T cells, are well established. However, the role of any B cell-derived factors is less clear, and it is possible that B cells regulate their own activation in an autocrine manner. The aim of this project was therefore to characterise the production and autocrine function of murine B cell-derived factors. B cells are observed to cluster upon activation in vitro, especially when stimulated via CD40, and B cell proliferation can be partially inhibited by blocking cell adhesion. It therefore appeared that B cell proximity was necessary for proliferation and this might have been due to the production of an autocrine growth factor. Here, a B cell autocrine growth factor activity was indeed demonstrated by separating cultures of B cells across dialysis tubing. This factor acted synergistically with CD40 stimulation. However, when B cells were cultured individually by embedding them in agarose, proliferation still occurred showing that B cell aggregation is not an absolute requirement for proliferation. An mRNA screen was performed in an attempt to identify cytokines produced by B cells upon activation. Several cytokine transcripts were discovered but none of these were strikingly upregulated following stimulation. Whilst tumour necrosis factor-α (TNF-α) has been reported to be a human B cell autocrine growth factor, murine B cells did not express TNF-α protein and TNF-α had no effect on murine B cell proliferation, activation or immunoglobulin secretion. Thus TNF-α is not an autocrine growth factor for murine B cells. Interleukin-6 was produced by murine B cells following activation, and this cytokine enhanced the survival of the B cells. Thus B cells clearly produce autocrine cytokines which regulate their activation.

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