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Gut Microbes. 2013 Mar-Apr;4(2):165-71. doi: 10.4161/gmic.23595. Epub 2013 Jan 18.

Impaired selection of IgA and intestinal dysbiosis associated with PD-1-deficiency.

Author information

1
Laboratory for Mucosal Immunity, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Japan.

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.

KEYWORDS:

IgA; PD-1; TFH; germinal center; gut; microbiota

PMID:
23333864
PMCID:
PMC3595078
DOI:
10.4161/gmic.23595
[Indexed for MEDLINE]
Free PMC Article

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