Open AccessLimited clonal relatedness between gut IgA plasma cells and memory B cells after oral immunization
Author(s) -
Mats Bemark,
Helena Hazanov,
Anneli Strömberg,
Rathan Joy Komban,
Joel Holmqvist,
Sofia Köster,
Johan Mattsson,
Per Sikora,
Ramit Mehr,
Nils Lycke
Publication year - 2016
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/ncomms12698
Subject(s) - memory b cell , germinal center , biology , immunology , antibody , b cell , immunization , naive b cell , cd11c , somatic hypermutation , cholera toxin , plasma cell , affinity maturation , immune system , microbiology and biotechnology , genetics , t cell , antigen presenting cell , phenotype , gene
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.