Abstract CCR10 is expressed by nearly all the intestinal IgA-producing plasma cells and was suggested to position these cells into the lamina propria. However, the in vivo function of CCR10 in the process is unclear and interfering with CCR10 or its ligand did not affect the intestinal IgA production under homeostatic conditions or during infection. Using CCR10-knockout/EGFP-knockin (CCR10EGFP/EGFP) mice we generated recently, we investigated expression and effect of CCR10 on IgA+ cells of different differentiation stages. We found that in the CCR10EGFP/EGFP mice IgA+ plasma cells were defective in migration to the intestine; but there was a compensational increase in generation of IgA+ plasma cells within intestinal isolated lymphoid follicles, resulting in normal levels of intestinal IgA production and increased localization of IgA+ plasma cells in bone marrow and other internal lymphoid organs under homeostatic conditions and in primary responses to the C. rodentium infection. In addition, the CCR10-deficiency also impaired maintenance of IgA+ memory B cells specifically in the intestine. As a result, IgA memory responses to the bacterial re-infection were severely compromised in the CCR10EGFP/EGFP mice. These findings demonstrate that CCR10 is critical in IgA memory responses by regulating migration and maintenance of IgA+ plasma cells and memory B cells and provide a mechanistic basis to manipulate the CCR10/ligand axis for the vaccine development against mucosal pathogens.