Mucosal or systemic microbiota exposures shape the B cell repertoire.

Li, Hai; Limenitakis, Julien Periclis Jean; Greiff, Victor; Yilmaz, Bahtiyar; Schären, Olivier Pascal; Urbaniak, Camilla; Zünd, Mirjam; Lawson, Melissa; Young, Ian D.; Rupp, Sandra; Heikenwälder, Mathias; McCoy, Kathleen; Hapfelmeier, Siegfried; Ganal-Vonarburg, Stephanie C.; Macpherson, Andrew J. (2020). Mucosal or systemic microbiota exposures shape the B cell repertoire. Nature, 584(7820), pp. 274-278. Springer Nature 10.1038/s41586-020-2564-6

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Colonization by the microbiota causes a marked stimulation of B cells and induction of immunoglobulin, but mammals colonized with many taxa have highly complex and individualized immunoglobulin repertoires1,2. Here we use a simplified model of defined transient exposures to different microbial taxa in germ-free mice3 to deconstruct how the microbiota shapes the B cell pool and its functional responsiveness. We followed the development of the immunoglobulin repertoire in B cell populations, as well as single cells by deep sequencing. Microbial exposures at the intestinal mucosa generated oligoclonal responses that differed from those of germ-free mice, and from the diverse repertoire that was generated after intravenous systemic exposure to microbiota. The IgA repertoire-predominantly to cell-surface antigens-did not expand after dose escalation, whereas increased systemic exposure broadened the IgG repertoire to both microbial cytoplasmic and cell-surface antigens. These microbial exposures induced characteristic immunoglobulin heavy-chain repertoires in B cells, mainly at memory and plasma cell stages. Whereas sequential systemic exposure to different microbial taxa diversified the IgG repertoire and facilitated alternative specific responses, sequential mucosal exposure produced limited overlapping repertoires and the attrition of initial IgA binding specificities. This shows a contrast between a flexible response to systemic exposure with the need to avoid fatal sepsis, and a restricted response to mucosal exposure that reflects the generic nature of host-microbial mutualism in the mucosa.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

UniBE Contributor:

Li, Hai; Limenitakis, Julien Periclis Jean; Yilmaz, Bahtiyar; Schären, Olivier Pascal; Zünd, Mirjam; Lawson, Melissa; Young, Ian David; Rupp, Sandra Carina; McCoy, Kathleen; Hapfelmeier, Siegfried Hektor; Ganal-Vonarburg, Stephanie Christine and Macpherson, Andrew

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1476-4687

Publisher:

Springer Nature

Language:

English

Submitter:

Rahel Fuhrer

Date Deposited:

23 Nov 2020 16:29

Last Modified:

23 Dec 2020 15:20

Publisher DOI:

10.1038/s41586-020-2564-6

PubMed ID:

32760003

BORIS DOI:

10.7892/boris.148424

URI:

https://boris.unibe.ch/id/eprint/148424

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