The memory B cell subset responsible for the secretory IgA response and protective humoral immunity to rotavirus expresses the intestinal homing receptor, α₄β₇

Infection of mice with murine rotaviruses induces life-long immunity, characterized by high levels of IgA in the intestine and large numbers of rotavirus (RV)-specific Ab-secreting cells in gut-associated lymphoid tissues. Lymphocyte trafficking into gut-associated lymphoid tissues is mediated by interaction of the α₄β₇ integrin on lymphocytes with the vascular mucosal addressin cell adhesion molecule-1. To determine whether B cell memory for RV correlates with α₄β₇ expression, we transferred sorted B220⁺ phenotypically defined memory (IgD^- α₄β₇(high) and IgD^- α₄β₇^-) and naive (IgD⁺ α₄β₇⁺) splenocytes into recombination- activating gene-2 knockout mice (B and T cell-deficient) that were chronically infected with RV. Only mice receiving α₄β₇(high) memory (IgD^-) B cells produced RV-specific IgA in the stool, cleared the virus, and were immune to reinfection. α₄β₇(high) (but not α₄β₇^-) memory B cells from donors boosted as much as 7 mo previously also cleared the virus, indicating that α₄β₇(high) memory B cells maintain long term functional immunity to RV. Although only α₄β₇(high) memory cells provided mucosal immunity, α₄β₇^- cells from recently boosted donor animals could generate RV-specific serum IgG, but, like naive (IgD⁺) B cells, were unable to induce viral clearance even 60 days after cell transfer. These data indicate that protective immunity for an intestinal pathogen, RV, resides in memory phenotype B cells expressing the intestinal homing receptor, α₄β₇.