Clonal persistence dominates homeostatic intestinal IgA responses

Immunity, vol. 58, pp. 3061–3074.e5

Abstract

Immunoglobulin A (IgA) is the most abundantly produced antibody isotype and mediates protection and homeostatic regulation at mucosal surfaces. Steady-state IgA production is supported by multiple pathways, including chronic germinal centers in gut inductive lymphoid tissues. However, we lack a detailed understanding of how IgA responses are temporally integrated across inductive and effector sites. Here, we dissect homeostatic IgA responses from the perspective of clonal repertoires in inductive compartments and the gut lamina propria as the main effector compartment. We show that unique clonal patterns dominate across gut inductive sites and that plasma cell (PC) clones in gut lamina propria entail progressive stages of differentiation. We demonstrate that ongoing diversification of recurrent clones continuously seeds the gut PC population. These observations suggest that clonal rather than cellular longevity shapes IgA responses and that dynamic modulation of recurrent clones may balance stability and flexibility of the gut PC repertoire.

Authors 8

1. Britta Simons Aachen Institute of Molecular Medicine

   RWTH Aachen University

   Affiliation as printed

   Institute of Molecular Medicine, RWTH Aachen University, Aachen, Germany

2. Atscharah Panyot Aachen Functional Microbiome Research Group Institute of Medical Microbiology

   RWTH Aachen University

   Affiliation as printed

   Functional Microbiome Research Group, Institute of Medical Microbiology, RWTH Aachen University, Aachen, Germany

3. Fabian Tobias Hager Aachen Institute of Molecular Medicine

   RWTH Aachen University

   Affiliation as printed

   Institute of Molecular Medicine, RWTH Aachen University, Aachen, Germany

4. Johanna Kabbert Aachen Institute of Molecular Medicine

   University of Copenhagen · RWTH Aachen University

   Affiliation as printed

   Institute of Molecular Medicine, RWTH Aachen University, Aachen, Germany; Department of Immunology and Microbiology, Skin Immunology Research Center, University of Copenhagen, Copenhagen, Denmark

5. Lydia Kopplin Aachen Institute of Molecular Medicine

   RWTH Aachen University

   Affiliation as printed

   Institute of Molecular Medicine, RWTH Aachen University, Aachen, Germany

6. Tim Rollenske

   University of Bern · University Hospital Bonn

   Affiliation as printed

   Institute of Molecular Medicine and Experimental Immunology, University Hospital Bonn, Bonn, Germany; Department for Biomedical Research, Visceral Surgery and Medicine, University of Bern, Bern, Switzerland; Multidisciplinary Center for Infectious Diseases, University of Bern, Bern, Switzerland

7. Thomas Clavel Aachen Functional Microbiome Research Group Institute of Medical Microbiology

   RWTH Aachen University

   Affiliation as printed

   Functional Microbiome Research Group, Institute of Medical Microbiology, RWTH Aachen University, Aachen, Germany

8. Oliver Pabst corresponding Aachen Institute of Molecular Medicine

   RWTH Aachen University

   Affiliation as printed

   Institute of Molecular Medicine, RWTH Aachen University, Aachen, Germany. Electronic address: opabst@ukaachen.de