In the present project the main question is which contribution B1 cells that mainly originate from the fetal liver are making to the gut-associated antibody response. To this end we made use of mice that express a transgenic l 2 immunoglobulin light chain. The B cells of such mice almost exclusively consist of B1 cells and exhibit a restricted antibody repertoire. Therefore, their heavy chain can be taken as molecular markers for B1 cells. So far we could show that B1 cells can be found in the germinal centers of the Peyers Patches although in these organs many cells can be found that express the endogenous light chain. This is unusual for the L2 mouse and could be due to receptor editing. Accordingly, in the present project we will investigate whether the microbial flora of the gut might induce B2 cells by receptor editing. In addition, we will study to what extent the microbial flora of the gut influences the antibody repertoire of B1 cells. These experiments will be extended by using bacterial pathogens with an intestinal port of entry. Furthermore, we will investigate what contribution B1 cells can make to the gut-associated humoral immunity when they have to compete with B2 cells. Finally, the potential of B1 cells to take part in the organogenesis of Peyers Patches will be investigated.