Ultra long-lived plasma cells in the human small intestine produce microbiota-reactive IgA antibodies
In: Beneficial MicrobesDepartment of Pathology, Oslo University Hospital-Rikshospitalet, Oslo, Norway
Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Manipal, Karnataka, India
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Norwegian PSC Research Center and Research Institute of Internal medicine, Division of Surgery, Inflammatory diseases and Transplantation, Oslo University Hospital, Oslo, Norway
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Norwegian PSC Research Center and Research Institute of Internal medicine, Division of Surgery, Inflammatory diseases and Transplantation, Oslo University Hospital, Oslo, Norway
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Department of Pathology, Oslo University Hospital-Rikshospitalet, Oslo, Norway
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Department of Hematology, Oslo University Hospital-Rikshospitalet, Oslo, Norway
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Department of Pathology, Oslo University Hospital-Rikshospitalet, Oslo, Norway
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Norwegian PSC Research Center and Research Institute of Internal medicine, Division of Surgery, Inflammatory diseases and Transplantation, Oslo University Hospital, Oslo, Norway
Section of Gatroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
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Department of Pathology, Oslo University Hospital-Rikshospitalet, Oslo, Norway
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Abstract
A large fraction of the intestinal microbiota is highly coated with secretory IgA, and bacteria-specific IgA is believed to shape the composition of the microbiota. A hallmark of the adaptive immune system is immunological memory to specific antigens. However, whether there is strong and persistent memory of secretory antibodies to bacterial antigens has not been determined. Here we show that ultra long-lived CD19–CD45– (age > 20 years) plasma cells (PCs) residing in the human small intestine produce IgA that binds to most taxa of a diverse anaerobic microbiota culture. Long-lived CD19–CD45+ (age > 10 years) and short-lived CD19+CD45+ (age < 2 years) PCs also produced IgA with broad bacterial reactivity. A clear correlation between high-binding and low-binding taxa was observed across the PC subsets. We also found that host PCs were depleted in acute intestinal graft versus host disease, a condition strongly associated with loss of microbiota diversity. Together, we show that bacterial antigens in the intestine induce an extremely stable, long-lasting humoral immune memory that may be important for the long-term stability and resilience of the intestinal microbiome.
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Ultra long-lived plasma cells in the human small intestine produce microbiota-reactive IgA antibodies
In: Beneficial MicrobesDepartment of Pathology, Oslo University Hospital-Rikshospitalet, Oslo, Norway
Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Manipal, Karnataka, India
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Norwegian PSC Research Center and Research Institute of Internal medicine, Division of Surgery, Inflammatory diseases and Transplantation, Oslo University Hospital, Oslo, Norway
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Norwegian PSC Research Center and Research Institute of Internal medicine, Division of Surgery, Inflammatory diseases and Transplantation, Oslo University Hospital, Oslo, Norway
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Department of Pathology, Oslo University Hospital-Rikshospitalet, Oslo, Norway
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Department of Hematology, Oslo University Hospital-Rikshospitalet, Oslo, Norway
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Department of Pathology, Oslo University Hospital-Rikshospitalet, Oslo, Norway
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Norwegian PSC Research Center and Research Institute of Internal medicine, Division of Surgery, Inflammatory diseases and Transplantation, Oslo University Hospital, Oslo, Norway
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Department of Pathology, Oslo University Hospital-Rikshospitalet, Oslo, Norway
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Abstract
A large fraction of the intestinal microbiota is highly coated with secretory IgA, and bacteria-specific IgA is believed to shape the composition of the microbiota. A hallmark of the adaptive immune system is immunological memory to specific antigens. However, whether there is strong and persistent memory of secretory antibodies to bacterial antigens has not been determined. Here we show that ultra long-lived CD19–CD45– (age > 20 years) plasma cells (PCs) residing in the human small intestine produce IgA that binds to most taxa of a diverse anaerobic microbiota culture. Long-lived CD19–CD45+ (age > 10 years) and short-lived CD19+CD45+ (age < 2 years) PCs also produced IgA with broad bacterial reactivity. A clear correlation between high-binding and low-binding taxa was observed across the PC subsets. We also found that host PCs were depleted in acute intestinal graft versus host disease, a condition strongly associated with loss of microbiota diversity. Together, we show that bacterial antigens in the intestine induce an extremely stable, long-lasting humoral immune memory that may be important for the long-term stability and resilience of the intestinal microbiome.
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