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Untersuchung der Lebenszeit von Plasmazellen nach der oralen Immunisierung von Musen

Lemke, A;

Plasma cells provide long-lasting humoral immunity by secretion of specific antibodies. After gastrointestinal application of antigens they are generated in gut-associated lymphoid tissue and their draining mesenteric lymph nodes. Depending on the antigen the spleen also participates in generation of intestinal induced plasma cells. The resulting plasma blasts predominantly express IgA isotype and migrate into the lamina propria of the small intestine. Secreted IgA antibodies are transported into the gut lumen where they specifically mark and neutralize pathogens and toxins, respectively. The results show that immunizing mice two times orally can induce antigen-specific plasma cells that can become long-lived within the lamina propria and bone marrow. Histologic investigations of the lamina propria regarding the incidence of known survival factors for plasma cells show that long-lived plasma cells do not co-localize with eosinophils as they doin bone marrow after systemic immunization (44). The survival factor APRIL is constitutively expressed in the lamina propria but analysis permit no preferential accumulation of plasma cells in APRIL-enriched regions. This observation can be explained by the presence of solu- ble APRIL in the lamina propria. Moreover, other factors might be part of the intestinal survival niche. Whereas the small intestine harbors long-lived plasma cells of the IgA isotype exclusively, IgA+ and IgG1+ plasma cells specific for orally administered antigens accumulate in the bone marrow. Both IgA+ and IgG1+ ASC persist in the bone marrow in survival niches while results imply that IgG1+ plasma cells are of considerable higher viability than IgA+ plasma cells. The results of this work show that intestinal induced plasma cells migrate to the bone marrow where they survive as long-lived plasma cells. They secrete specific antibodies for several months and thereby provide a constant serum titer.