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Nature. 2019 Jul;571(7763):122-126. doi: 10.1038/s41586-019-1285-1. Epub 2019 Jun 12.

Migrant memory B cells secrete luminal antibody in the vagina.

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Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki City, Japan.
Immunology Frontier Research Center, Osaka University, Ibaraki City, Japan.
Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA.
Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
Department of Molecular Cellular and Developmental Biology, Yale University, New Haven, CT, USA.
Howard Hughes Medical Institute, Chevy Chase, MD, USA.


Antibodies secreted into mucosal barriers serve to protect the host from a variety of pathogens, and are the basis for successful vaccines1. In type I mucosa (such as the intestinal tract), dimeric IgA secreted by local plasma cells is transported through polymeric immunoglobulin receptors2 and mediates robust protection against viruses3,4. However, owing to the paucity of polymeric immunoglobulin receptors and plasma cells, how and whether antibodies are delivered to the type II mucosa represented by the lumen of the lower female reproductive tract remains unclear. Here, using genital herpes infection in mice, we show that primary infection does not establish plasma cells in the lamina propria of the female reproductive tract. Instead, upon secondary challenge with herpes simplex virus 2, circulating memory B cells that enter the female reproductive tract serve as the source of rapid and robust antibody secretion into the lumen of this tract. CD4 tissue-resident memory T cells secrete interferon-γ, which induces expression of chemokines, including CXCL9 and CXCL10. Circulating memory B cells are recruited to the vaginal mucosa in a CXCR3-dependent manner, and secrete virus-specific IgG2b, IgG2c and IgA into the lumen. These results reveal that circulating memory B cells act as a rapidly inducible source of mucosal antibodies in the female reproductive tract.

[Available on 2019-12-12]

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