Mucosal Addressin Cell-Adhesion Molecule-1 Controls Plasma-Cell Migration and Function in the Small Intestine of Mice

Background & Aims: Immunoglobulin (Ig) A secretion into the intestinal lumen is an important immune mechanism of the gastrointestinal (GI) tract. B cells proliferate and differentiate into IgA-secreting plasma cells (PC) within lymphoid organs then migrate directly into the intestinal lamina propria. We aimed to elucidate the in vivo role of the mucosal addressin cell-adhesion molecule-1 (MAdCAM-1), which is constitutively expressed in the GI-associated lymphoid tissue, in B-cell migration. Methods: We generated MAdCAM-1-deficient mice (MAdCAMΔ) and evaluated the B-cell compartment of the GI-associated lymphoid tissue. We also assessed PC migration to the small intestine and the intestinal immune response after oral immunization. Results: In MAdCAMΔ mice, the size of Peyer's patches was drastically reduced, compared with that of wild-type mice; this difference was detectable by 3 days after birth, indicating that MAdCAM-1 is dispensable for embryonic Peyer's patch development but mediates recruitment of lymphocytes into this lymphoid organ at later stages. Moreover, antigen-specific, IgA-positive PC were severely compromised in their migration to the small intestine; accordingly, there was a reduced number of IgA-secreting PC in the lamina propria of the small intestine. The MAdCAMΔ mice were unable to mount a normal intestinal IgA response after oral immunization with cholera toxin. Conclusion: These data provide in vivo evidence that MAdCAM-1 is required for the localization and function of IgA-secreting PC in the intestine. © 2009 AGA Institute.