Two distinctive pathways for recruitment of naive and primed IgM+ B cells to the gut lamina propria

Intestinal IgA(+) B cells are generated from IgM(+) B cells by in situ class switching in two separate gut microenvironments: organized follicular structures and lamina propria (LP). However, the origin of IgM(+) B cells in the gut LP is unknown. Transfer experiments to reconstitute IgM(+) B cells and IgA plasma cells in LP of aly/aly mice, which are defective in all organized follicular structures because of an NF-kappaB-inducing kinase (NIK) mutation, revealed that naive B cells can directly migrate to the LP. This migration requires NIK-dependent activation of gut stromal cells. By contrast, the entry of gut-primed IgM(+) B cells to the LIP is independent of stromal cells with functional NIK. Our results indicate that naive B cells directly migrate to the LIP by a distinct pathway from gut-primed B cells.