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The majority of intestinal IgA+ and IgG+ plasmablasts in the human gut are antigen-specific
Julia Benckert, … , Bertram Wiedenmann, Hedda Wardemann
Julia Benckert, … , Bertram Wiedenmann, Hedda Wardemann
Published April 1, 2011
Citation Information: J Clin Invest. 2011;121(5):1946-1955. https://doi.org/10.1172/JCI44447.
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Research Article Immunology

The majority of intestinal IgA+ and IgG+ plasmablasts in the human gut are antigen-specific

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Abstract

Mucosal antibody responses play a major role in mediating homeostasis with the intestinal flora. It has been suggested that imbalance in the IgA+ and IgG+ intestinal B cell repertoire may be associated with the development of diseases such as inflammatory bowel disease. Despite this, little is known about the antibody specificity of human intestinal plasmablasts. Here, we have determined the reactivity profile of single isolated IgA+ and IgG+ plasmablasts from human terminal ileum using antibody cloning and in vitro expression. We found that approximately 25% of intestinal IgA and IgG plasmablast antibodies were polyreactive; the majority were antigen-specific. Antigen specificity was not only directed against enteropathogenic microbes but also against commensal microbes and self antigens. Regardless of their reactivity, all intestinal antibodies were somatically mutated and showed signs of antigen-mediated selection, suggesting that they developed from antigen-specific B cell responses. Together, our data indicate that antigen-specific immune responses to intestinal microbes are largely responsible for the maintenance of intestinal homeostasis and thus provide a basis for understanding the deregulated immune responses observed in patients with inflammatory bowel disease.

Authors

Julia Benckert, Nina Schmolka, Cornelia Kreschel, Markus Josef Zoller, Andreas Sturm, Bertram Wiedenmann, Hedda Wardemann

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Figure 5

Antibody reactivity of human IgA+ and IgG+ lamina propria plasmablasts.

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Antibody reactivity of human IgA+ and IgG+ lamina propria plasmablasts.
...
Pie charts summarize the frequency of IgA+ and IgG+ plasmablasts of unknown specificity (white), of plasmablasts with specificity for intestinal microbes (blue, E. coli; yellow, M. morganii; red, E. cloacae; green, rotavirus) or self antigens (light gray, HEp-2 or intestinal tissue), and of unspecific bacteria-reactive (hatched dark gray) and polyreactive (black) plasmablasts as percentages of all tested IgA and IgG antibodies, respectively, from HD1–HD3. The number of tested antibodies is indicated in the pie chart centers.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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