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 LP is independent of stromal cells with functional NIK. Our results indicate that naive B cells directly migrate to the LP by a distinct pathway from gut-primed B cells.