Antigen-specific B-cell unresponsiveness induced by chronic Mycobacterium avium subsp. paratuberculosis infection of cattle

Mycobacterium avium subsp. paratuberculosis infection of cattle results in a chronic granulomatous enteritis. Clinical disease (i.e., cachexia, diarrh ea, and high fecal bacterial counts) is preceded by a lengthy subclinical s tage of disease. The immunologic mechanisms associated with the progression of infected cattle from subclinical to clinical disease are unclear. In th is study, a cell proliferation assay was used in combination with flow cyto metry to compare peripheral blood lymphocyte responses of cattle,vith subcl inical paratuberculosis to responses of cattle with clinical paratuberculos is. B cells from cattle with subclinical disease proliferated vigorously up on stimulation with M. avium subsp. paratuberculosis antigen, with up to 12 .4% of the total B cells responding. However, B cells from cattle with clin ical disease did not proliferate upon antigen stimulation despite good prol iferation in response to concanavalin A stimulation. In addition, these ani mals had high percentages of peripheral blood B cells. B cells from noninfe cted animals did not proliferate upon M. avium subsp. paratuberculosis anti gen stimulation. Thus, it appears that B-cell proliferation is a sensitive indicator of subclinical Johne's disease. Furthermore, the immunologic mech anisms responsible for the antigen-specific unresponsiveness of peripheral blood B cells may be significant in the eventual progression from subclinic al to clinical Johne's disease in cattle.