Asymmetric Recirculation of α4β7-expressing Memory B Cells throughout the Gut-associated Lymphoid Tissues

Memory B cells (MBCs) are important for secondary humoral responses, but their homing properties are largely unknown. We previously showed that immunization by the intra-rectal route induces IgA antibody-secreting cells (ASCs) which express high levels of the integrin α₄β₇ and migrate not only to the colon but also to the small intestine. Here we investigate the distribution of MBCs induced by intra-rectal immunization with a particulate antigen in comparison with other immunization routes. We identified MBCs in secondary lymphoid organs of immunized mice as isotype-switched B cells (B220⁺, sIgD^-, sIgG₁/sIgA⁺) that lack germinal center-specific markers (GL7^-, CD38⁺) and bind to fluorescent antigen. Whereas only ~40% of antigen-specific MBCs induced by subcutaneous or intra-nasal immunization express α₄β₇, virtually all MBCs induced by intra-rectal immunization are α₄β₇⁺. Therefore, antigen-specific MBCs induced by intra-rectal immunization preferentially recirculate among the gut-associated lymphoid tissues (GALTs), such as Peyer’s patches (PPs) and mesenteric lymph nodes (MLNs), which express MAdCAM-1, but are instead largely excluded from extra-intestinal LNs. When mice deficient for β₇-integrin were immunized by the intra-rectal route, MBCs were reduced in MLNs and increased in peripheral LNs. Likewise, adoptive transfer of antigen-specific MBCs from β₇-deficient mice immunized by the intra-rectal route generated fewer antigen-specific ASCs in PPs of recipient mice upon rechallenge, but higher number of ASCs in spleen, in comparison with MBCs from normal mice. In contrast, after intra-nasal immunization, antigen-specific cells were instead significantly increased in MLNs of β₇-deficient mice, suggesting that competition among lymphocytes is important for MBC homing towards the GALTs.