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Impaired selection of IgA and intestinal dysbiosis associated with PD-1-deficiency.
- Source :
-
Gut microbes [Gut Microbes] 2013 Mar-Apr; Vol. 4 (2), pp. 165-71. Date of Electronic Publication: 2013 Jan 18. - Publication Year :
- 2013
-
Abstract
- A major function of immunoglobulin A (IgA) is to maintain balanced bacterial communities in the gut. We have previously shown that diversification of IgA upon somatic hypermutation (SHM) is critical for IgA function yet the principles governing the selection of IgA in the gut have remained elusive. Here we discuss recent progress in understanding this process as revealed by our studies in mice that lack the inhibitory co-receptor programmed cell death-1 (PD-1). We found that PD-1 affects the dynamics of germinal center (GC) B cells by controlling the number and the nature of T helper cells in the Peyer's patches (PPs). Deregulation of the T cell compartment impacts the selection of IgA plasma cells leading to gut dysbiosis. When the PD-1-dependent checkpoint is missing, gut bacteria go beyond the mucosal barrier and induce systemic GCs that can generate antibodies with auto-reactive properties.
- Subjects :
- Animals
B-Lymphocytes immunology
Germinal Center immunology
Immunity, Mucosal
Mice
Mice, Knockout
Peyer's Patches immunology
Programmed Cell Death 1 Receptor
T-Lymphocytes immunology
Antigens, Differentiation genetics
Antigens, Differentiation immunology
Gastrointestinal Tract immunology
Gastrointestinal Tract microbiology
Immunoglobulin A immunology
Metagenome immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1949-0984
- Volume :
- 4
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Gut microbes
- Publication Type :
- Academic Journal
- Accession number :
- 23333864
- Full Text :
- https://doi.org/10.4161/gmic.23595