I completed the first part of my project focused on understanding how memory B cells develop in the gut after a Salmonella infection. Using a reporter mouse, I tracked these cells by flow cytometry in different organs including spleen, mesenteric lymph nodes, Peyer’s patches and Lamina propria, at different times after oral infection. I analyzed the isotype expression among memory B cell populations as well as the specificity of LLPCs by Elispot. However, the results didn't match what we expected. Unlike in the lungs, I didn’t find a significant number of memory B cells in the lamina propria. Because of this, we decided not to continue with the next phases of the project, which were originally planned to focus on characterizing these B cells. Instead, we shifted our focus to compare the different strategies adopted by the gut and lungs to respond to secondary infections. To do this, we added influenza infection as part of the project and study the immune response in the lungs and lymph nodes in order to be able to compare with salmonella infection in the gut. We discovered that the lungs and gut have different strategies for dealing with secondary infections: the lungs rely mostly on memory B cells, while the gut mainly uses long-lived plasma cells (LLPCs). By infecting mice with different load of bacteria (germ-free vs SPF mice) we found that in the gut, unlike in the lungs, the presence of microbes triggers the production of TGF-β, a cytokine that favors B cells switch to IgA. To go deeper in the analysis of IgA response in both mucosal tissues we used different transgenic mouse models and observed that the expression of IgA on B cells, regardless their affinity, pushes them towards becoming LLPCs by modulating downstream signaling. This means that the microbial status could shape the long-term strategies adopted by each mucosa.
