Chemokine receptor CCR10 is expressed by all intestinal
IgA-producing plasma cells and is suggested to play an important role in positioning these cells in the lamina propria for proper
IgA production to maintain intestinal homeostasis and protect against
infection. However, interfering with CCR10 or its
ligand did not impair intestinal
IgA production under homeostatic conditions or during
infection, and the in vivo function of CCR10 in the intestinal
IgA response remains unknown. We found that an enhanced generation of
IgA(+) cells in isolated lymphoid follicles of intestines offset defective intestinal migration of
IgA(+) cells in CCR10-KO mice, resulting in the apparently normal
IgA production under homeostatic conditions and in primary response to pathogen
infection. However, the compensatorily generated
IgA(+) cells in CCR10-KO mice carried fewer hypermutations in their Ig heavy chain alleles than those of WT mice, indicating that their
IgA repertoires are qualitatively different, which might impact the intestinal homeostasis of microflora. In addition, CCR10-deficient long-lived
IgA-producing plasma cells and
IgA(+) memory B cells generated against the pathogen
infection could not be maintained properly in intestines. Consequently,
IgA memory responses to the pathogen
reinfection were severely impaired in CCR10-KO mice. These findings elucidate critical roles of CCR10 in regulating the intestinal
IgA response and memory maintenance and could help in design of
vaccines against intestinal and possibly other mucosal pathogens.