SPIRALIN, A MYCOPLASMAL MEMBRANE LIPOPROTEIN, INDUCES T-CELL-INDEPENDENT B-CELL BLASTOGENESIS AND SECRETION OF PROINFLAMMATORY CYTOKINES

Mycoplasmas are bacteria which can cause respiratory, arthritic, and u rogenital diseases. During the early phase of infection, mycoplasmas u sually induce an inflammatory response and a humoral response preferen tially directed against their membrane-bound, surface-exposed lipoprot eins. In this report, we describe the effects on immune cells of spira lin, a well-characterized mycoplasmal lipoprotein. Purified spiralin s timulated the in vitro proliferation of human peripheral blood mononuc lear cells and murine splenocytes. The stimulation pathway was probabl y different from that followed by Escherichia coli lipopolysaccharide because the effect of spiralin was not abolished by polymyxin B. Compa rison of the effects of whole, native spiralin with those induced by p roteinase K-digested spiralin or by the C-terminal half of spiralin (p eptide p[13.5](T)) revealed that the first half of the protein, which contains the lipoylated N terminus, is responsible for the mitogenic a ctivity. In contrast to whole spiralin, proteinase K-digested spiralin did not trigger murine B-cell differentiation and immunoglobulin G an d M secretion. Stimulation of human or murine immune cells led to earl y secretion of proinflammatory cytokines (human tumor necrosis factor alpha and murine interleukin 1 or 6). Spiralin induced the T-cell-inde pendent blastogenesis of murine B cells but did not stimulate T cells. Altogether, our data demonstrate that spiralin possesses potent immun ostimulating activity, similar to that reported for lipoproteins of pa thogenic gracilicutes (gram-negative eubacteria; e.g., Borrelia burgdo rferi OspA and E. coli Braun lipoprotein), and are consistent with the fact that lipoproteins are major antigens during mycoplasma infection s.