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

Publication date: 5 September 2017
Source:Cell Reports, Volume 20, Issue 10
Author(s): 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
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.

Graphical abstract

Teaser

The relationship between mucosal antibody responses and antibodies in blood is not clearly understood. Iversen et al. use proteomics to characterize antibodies in serum and gut biopsy specimens obtained from celiac disease patients. Serum and gut IgA are derived from the same B cell clones but produced by different plasma cells.


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