Congratulations to our Director and Platform 1 Lead Dr. Kathy McCoy on this recent publication!
In this intercontinental research effort between Switzerland, Norway, Germany and Canada, Dr. H. Li, colleagues and international collaborators notably Dr. K.D. McCoy, used “localized time-limited exposures of defined doses of single benign microbial taxa in germ-free mice” to “address how the B cell repertoire is shaped by microbiota exposure at mucous membranes or in systemic lymphoid tissues, and how interactions between different exposure sites or subsequent exposures to different taxa affect the outcome”.
“Our data show for the first time that not only the composition of our intestinal microbiota, but also the timing and sequence of exposure to certain members of the commensal microbiota, happening predominantly during the first waves of colonisations during early life, have an outcome on the resulting B cell receptor repertoire and subsequent immunity to pathogens.”
Dr. Hai Li
Abstract
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 repertoires. Here we use a simplified model of defined transient exposures to different microbial taxa in germ-free mice 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.
Read more about this breakthrough in the press release here and in the paper here.
Publication: Mucosal or systemic microbiota exposures shape the B cell repertoire. Li H, Limenitakis JP, Greiff V, Yilmaz B, Scharen O, Urbaniak C, Zund M, Lawson MAE, Young ID, Rupp S, Heikenwalder M, McCoy KD, Hapfelmeier S, Ganal-Vonarburg SC, Macpherson AJ. Nature. 05 August 2020.
