engleski

Interleukin-12 is a potent inducer of phenotypic changes but not of antigen presentation capacity in human B lymphocytes.

IL-12 recently has been described to enhance Ig production of mitogen-activated human B cells. In the present study we studied the ability of IL-12 to modulate the growth, phenotype and antigen presentation capacity of human resting B lymphocytes. Resting B cells express low levels of costimulatory molecules, B7-1 (CD80) and B7-2 (CD86), and as such can activate only momory T cells and tolerize naive T cells. Inefficient antigen presentation of resting B cells can be overcome by signals through surface immunoglobulin (sIg), MHC-II and CD40 and also by cytokines such as IL-4 and IFN-gamma. We observed that IL-12 did not influence the growth of highly purified tonsillar resting B cells after co-ligation of sIgM and CD40, but induced significant phenotypic changes including downregulation of CD23 and CD5, and upregulation of CD38. These phenotypic changes in BCR/CD40 stimulated B cells could also be induced by IFN-gamma but these effects of the two cytokined were not additive. Coligation of sIgM and CD40 dramatically upregulated both CD80 and CD86 in the aabsence of exogenous cytokines. IL-12 and to a greather extent IFN-gamma, induced CD86 on unstimulated B cells and further upregulated CD86 expression on sIgM-stimulated cells, while IL-4 upregulated both CD80 and CD86. However, whereas IL-4 and IFN-gamma were able to enhance proliferation of allogeneic T cells by B cells preactivated with anti-mu mAb, IL-12 was inactive in this regard. We found that IL-10 was able to inhibit IL-12 induced CD86 expression but had no effect on IL-4 and IFN-gamma mediated induction of B7 molecules. Neutralising anti-IFN-gamma mAb blocked the effects of IL-12 on expression of CD5, CD23, CD38 and CD86 suggesting that they were mediated indirectly by autocrine effects of IFN-gamma. Our data suggest that the role of IL-12 in B cell responsiveness is limited to the induction of phenotypic features associated with B cell differentiation and not in enhancement of the B cell's antigen presenting function.

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