α4β7 integrin/MAdCAM-1 adhesion pathway is crucial for B cell migration into pancreatic lymph nodes in nonobese diabetic mice

Although B cells are crucial antigen-presenting cells in the initiation of T cell autoimmunity to islet β cell autoantigens in type 1 diabetes (T1D), adhesion molecules that control migration of B cells into pancreatic lymph nodes (PanLN) in the nonobese diabetic (NOD) mouse model of human T1D have not been defined. In this study, we found that B cells from PanLN of 3–4-week-old female NOD mice expressed high levels of α4 integrin and LFA-1 and intermediate levels of β7 integrin; half of B cells were L-selectinhigh. In short-term in vivo lymphocyte migration assays, B cells migrated from the bloodstream into PanLN more efficiently than into peripheral LNs. Moreover, antibodies to mucosal addressin cell adhesion molecule 1 (MAdCAM-1) and α4β7 integrin inhibited >90% of B cell migration into PanLN. In contrast, antibodies to peripheral node addressin, L-selectin or LFA-1 partially inhibited B cell migration into PanLN. Furthermore, one intraperitoneal injection of anti-MAdCAM-1 antibody into 3-week-old NOD mice significantly inhibited entry of B cells into PanLN for at least 2 weeks. Taken together, these results indicate that the α4β7 integrin/MAdCAM-1 adhesion pathway plays a predominant role in migration of B cells into PanLN in NOD mice. Thus, specific blockage of α4β7 integrin/MAdCAM-1 adhesion pathway-mediated B cell migration may be a potential treatment for T1D.