Identification and Use of Protective Monoclonal IgA Antibodies Against Viral and Bacterial Pathogens

Neutra, Marian R.; Weltzin, Richard; Winner, Louis; Mack, Julie; Michetti, Pierre; Morrison, Lynda A.; Fields, Bernard N.; Mekalanos, John J.; Kraehenbuhl, Jean–Pierre

doi:10.1007/978-1-4615-3838-7_22

Cited by 4 publications

(1 citation statement)

References 17 publications

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“…The production of secretory IgA depends on bacterial colonization of the gastrointestinal tract (3,4). Secretory IgA plays a major role in mediating immune exclusion of luminal antigens and homeostasis with the intestinal flora as well as protection against invading pathogens (5)(6)(7)(8)(9). Binding of secretory IgA to intestinal foreign antigens promotes the controlled antigen sampling of microbial and food antigens by microfold cells within the epithelial layer and helps to prevent attachment of microbes to the epithelium and clearance of microbes, which have breached the epithelial barrier (10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

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

Benckert¹,

Schmolka²,

Kreschel³

et al. 2011

J. Clin. Invest.

227

224

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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.

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