Strong Clonal Relatedness between Serum and Gut IgA despite Different Plasma Cell Origins

Rasmus Iversen; Omri Snir; Maria Stensland; José E Kroll; Øyvind Steinsbø; Ilma R Korponay-Szabó; Knut E A Lundin; Gustavo A de Souza; Ludvig M Sollid

doi:10.1016/j.celrep.2017.08.036

Strong Clonal Relatedness between Serum and Gut IgA despite Different Plasma Cell Origins

Cell Rep. 2017 Sep 5;20(10):2357-2367. doi: 10.1016/j.celrep.2017.08.036.

Authors

Rasmus Iversen¹, Omri Snir¹, Maria Stensland², José E Kroll³, Øyvind Steinsbø¹, Ilma R Korponay-Szabó⁴, Knut E A Lundin⁵, Gustavo A de Souza⁶, Ludvig M Sollid⁷

Affiliations

¹ Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, NO-0372 Oslo, Norway.
² Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, NO-0372 Oslo, Norway; Proteomics Core Facility, Oslo University Hospital-Rikshospitalet, NO-0372 Oslo, Norway.
³ Brain Institute, Federal University of Rio Grande do Norte, RN 59056-450 Natal, Brazil.
⁴ Celiac Disease Center, Heim Pál Children's Hospital, HU-1089 Budapest, Hungary.
⁵ Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, NO-0372 Oslo, Norway; Department of Gastroenterology, Oslo University Hospital-Rikshospitalet, NO-0372 Oslo, Norway; KG Jebsen Coeliac Disease Research Centre, University of Oslo, NO-0372 Oslo, Norway.
⁶ Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, NO-0372 Oslo, Norway; Proteomics Core Facility, Oslo University Hospital-Rikshospitalet, NO-0372 Oslo, Norway; Brain Institute, Federal University of Rio Grande do Norte, RN 59056-450 Natal, Brazil.
⁷ Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, NO-0372 Oslo, Norway; KG Jebsen Coeliac Disease Research Centre, University of Oslo, NO-0372 Oslo, Norway. Electronic address: l.m.sollid@medisin.uio.no.

Abstract

Mucosal antigens induce generation of lamina propria plasma cells (PCs) that secrete dimeric immunoglobulin A (IgA) destined for transport across the epithelium. In addition, blood contains monomeric IgA. To study the relationship between mucosal and systemic antibody responses, we took advantage of celiac disease patient samples for isolation of gut PCs as well as serum IgA and IgG reactive with a gluten-derived peptide or the autoantigen transglutaminase 2. Proteomic analysis of serum IgA revealed antigen-specific V-gene preferences, which matched those found in gut PCs. Further, gut PC CDR-H3 sequences were abundant in serum IgA but also detectable in serum IgG. Our data indicate that the same B cell clones that give rise to gut PCs also contribute to the serum antibody pool. However, serum IgA antibodies had a molecular composition distinct from that of IgA antibodies secreted in the gut, suggesting that individual B cell clones give rise to different PC populations.

Keywords: antibodies; autoimmunity; celiac disease; mass spectrometry; mucosal immune system; next-generation sequencing; plasma cells; proteomics.

MeSH terms

Adult
Child, Preschool
GTP-Binding Proteins / immunology
Humans
Immunity, Mucosal / physiology
Immunoglobulin A / metabolism*
Immunoglobulin G / metabolism
Infant
Mass Spectrometry
Plasma Cells / metabolism*
Prospective Studies
Protein Glutamine gamma Glutamyltransferase 2
Proteomics
Transglutaminases / immunology

Substances

Immunoglobulin A
Immunoglobulin G
Protein Glutamine gamma Glutamyltransferase 2
Transglutaminases
GTP-Binding Proteins

Grants and funding

268541/ERC_/European Research Council/International