Description |
Borrelia burgdorferi produces potent cellular activating molecules capable of stimulating polyclonal proliferation and immunoglobulin production by murine B lymphocytes and cytokine production by a variety of cell types. These stimulatory molecules function in infected mice, resulting in elevated levels of circulating immunoglobulins and serum IL-6. We have recently demonstrated that the purified outer surface lipoproteins, OspA and OspB, possess these properties. To assess their possible involvement in human disease we determined if cells from normal human donors could respond to these activities. Normal human B lymphocytes, but not T lymphocytes, proliferated when incubated with either sonicated B. burgdorferi or with OspA. Sonicated B. burgdorferi was efficient at stimulating IgM production by human mononuclear cell cultures; however, purified OspA was relatively inactive. Both sonicated B. burgdorferi and purified OspA stimulated production of high levels of Il-6 by mononuclear cells. These findings extend our observation with the mouse, and suggest that the stimulatory lipoproteins could indeed be involved in the symptoms and pathologies of human disease. Furthermore, we hypothesized that the difference in cytokine levels in infected mice of different strains could relate to the difference in the IF-1 locus, which controls the production of IFN-?, IFN-?, TNF, IL-1 and IL-6. The IF-1 locus may control the response of cell of OSPA/B. So far, we have failed to detect differences in the response to OSPA/B between the cells from IF-1h and IF-1(1) strains. This may indicate a limitation to our method of analysis or a need to modify our hypothesis to include complex interactions occurring within the infected mouse. |