The memory B cell subset responsible for the secretory IgA response and protective humoral immunity to rotavirus expresses the intestinal homing receptor, alpha4beta7.
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 alpha4beta7 integrin on lymphocytes with the vascular mucosal addressin cell adhesion molecule-1. To determine whether B cell memory for RV correlates with alpha4beta7 expression, we transferred sorted B220+ phenotypically defined memory (IgD- alpha4beta7(high) and IgD- alpha4beta7-) and naive (IgD+ alpha4beta7+) splenocytes into recombination-activating gene-2 knockout mice (B and T cell-deficient) that were chronically infected with RV. Only mice receiving alpha4beta7(high) memory (IgD-) B cells produced RV-specific IgA in the stool, cleared the virus, and were immune to reinfection. Alpha4beta7(high) (but not alpha4beta7-) memory B cells from donors boosted as much as 7 mo previously also cleared the virus, indicating that alpha4beta7(high) memory B cells maintain long term functional immunity to RV. Although only alpha4beta7(high) memory cells provided mucosal immunity, alpha4beta7- 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, alpha4beta7.
Department of Pathology, Digestive Disease Center, Stanford University, CA 94305, USA. mwilliam@cmgm.stanford.edu
M B
MB
Williams
J R
JR
Rosé
L S
LS
Rott
M A
MA
Franco
H B
HB
Greenberg
E C
EC
Butcher
D000818:Animals; D000917:Antibody Formation; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D018928:Immunity, Mucosal; D007156:Immunologic Memory; D016023:Integrins / Q000276:immunology*; D007422:Intestines / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000276:immunology*
D000956:Antigens, Viral; D016023:Integrins; C071777:integrin alpha4beta7