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

	Text s41586-020-2564-6 (1).pdf - Published Version Restricted to registered users only Available under License Publisher holds Copyright. Download (20MB) | Request a copy
Preview	Text Li_et_al._2020_preprint_red.pdf - Accepted Version Available under License Publisher holds Copyright. Download (1MB) | Preview

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.

Interest & Impact

Downloads

33 since deposited on 23 Nov 2020
26 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item