THE MEMORY B-CELL SUBSET RESPONSIBLE FOR THE SECRETORY IGA RESPONSE AND PROTECTIVE HUMORAL IMMUNITY TO ROTAVIRUS EXPRESSES THE INTESTINAL HOMING RECEPTOR, ALPHA(4)BETA(7)

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 lymph oid tissues. Lymphocyte trafficking into gut-associated lymphoid tissu es is mediated by interaction of the alpha(4)beta(7) integrin on lymph ocytes with the vascular mucosal addressin cell adhesion molecule-1. T o determine whether B cell memory for RV correlates with alpha(4)beta( 7) expression, we transferred sorted B220(+) phenotypically defined me mory (IgD(-) alpha(4)beta(7)(high) and IgD(-) alpha(4)beta(7)(-)) :ind naive (IgD(+)alpha(4)beta(7)(+)) splenocytes into recombination-activ ating gene-2 knockout mice (B and T cell-deficient) that were chronica lly infected with RV, Only mice receiving alpha(4)beta(7)(high) memory (IgD(-))B cells produced RV-specific IgA in the stool, cleared the vi rus, and were immune to reinfection. alpha(4)beta(7)(high) (but not al pha(4)beta(7)(-)) memory B cells from donors boosted as much as 7 mo p reviously also cleared the virus, indicating that alpha(4)beta(7)(high ) memory B cells maintain long term functional immunity to RV, Althoug h only alpha(4)beta(7)(high) memory cells provided mucosal immunity, a lpha(4)beta(7)(-) cells from recently boosted donor animals could gene rate KV-specific serum IgG, but, like naive (IgD(+)) B cells, were una ble 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, alpha(4)beta(7).