Limited clonal relatedness between gut IgA plasma cells and memory B cells after oral immunization.
Understanding how memory B cells are induced and relate to long-lived plasma cells is important for vaccine development. Immunity to oral vaccines has been considered short-lived because of a poor ability to develop IgA B-cell memory. Here we demonstrate that long-lived mucosal IgA memory is readily achieved by oral but not systemic immunization in mouse models with NP hapten conjugated with cholera toxin and transfer of B1-8(high)/GFP(+) NP-specific B cells. Unexpectedly, memory B cells are poorly related to long-lived plasma cells and less affinity-matured. They are α4β7-integrin(+)CD73(+)PD-L2(+)CD80(+) and at systemic sites mostly IgM(+), while 80% are IgA(+) in Peyer's patches. On reactivation, most memory B cells in Peyer's patches are GL7(-), but expand in germinal centres and acquire higher affinity and more mutations, demonstrating strong clonal selection. CCR9 expression is found only in Peyer's patches and appears critical for gut homing. Thus, gut mucosal memory possesses unique features not seen after systemic immunization.
Mucosal Immunobiology and Vaccine Research Center and the Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, S-405-30 Gothenburg, Sweden.|Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, S-405-30 Gothenburg, Sweden.
Mats
0000-0001-7416-9819
M
Bemark
Computational Immunology Lab, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, 5290002 Ramat-Gan, Israel.
Helena
H
Hazanov
Mucosal Immunobiology and Vaccine Research Center and the Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, S-405-30 Gothenburg, Sweden.
Anneli
A
Strömberg
Mucosal Immunobiology and Vaccine Research Center and the Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, S-405-30 Gothenburg, Sweden.
Rathan
R
Komban
Mucosal Immunobiology and Vaccine Research Center and the Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, S-405-30 Gothenburg, Sweden.
Joel
J
Holmqvist
Mucosal Immunobiology and Vaccine Research Center and the Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, S-405-30 Gothenburg, Sweden.
Sofia
S
Köster
Mucosal Immunobiology and Vaccine Research Center and the Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, S-405-30 Gothenburg, Sweden.
Johan
J
Mattsson
Department of Laboratory Medicine, Sahlgrenska University Hospital, S-405-30 Gothenburg, Sweden.
Per
P
Sikora
Computational Immunology Lab, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, 5290002 Ramat-Gan, Israel.
Ramit
R
Mehr
Mucosal Immunobiology and Vaccine Research Center and the Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, S-405-30 Gothenburg, Sweden.|Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, S-405-30 Gothenburg, Sweden.
Nils Y
NY
Lycke
D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial; D001402:B-Lymphocytes / Q000502:physiology*; D002772:Cholera Toxin / Q000276:immunology*; D005260:Female; D041981:Gastrointestinal Tract / Q000166:cytology* / Q000276:immunology; D007070:Immunoglobulin A / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007156:Immunologic Memory; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010950:Plasma Cells / Q000502:physiology*
D000907:Antibodies, Bacterial; D007070:Immunoglobulin A; D002772:Cholera Toxin