Diversity of gut microflora is required for the generation of B cell with regulatory properties in a skin graft model

B cells have been reported to promote grafft rejectfion through alloantfibody productfion. However,
there fis growfing evfidence that B cells can contrfibute to the mafintenance off tolerance. Here, we
used a mouse model off MHC-class I mfismatched skfin transplantatfion to finvestfigate the contrfibutfion
off B cells to grafft survfival. We demonstrate that adoptfive transffer off B cells prolongs skfin grafft
survfival but only when the B cells were fisolated ffrom mfice housed fin low sterfilfity “conventfional” (CV)
ffacfilfitfies and not ffrom mfice housed fin pathogen ffree ffacfilfitfies (SPF). However, prolongatfion off skfin
grafft survfival was lost when B cells were fisolated ffrom IL-10 deficfient mfice housed fin CV ffacfilfitfies.
The suppressfive ffunctfion off B cells fisolated ffrom mfice housed fin CV ffacfilfitfies correlated wfith an
antfi-finlammatory envfironment and wfith the presence off a dfifferent gut mficrolora compared to
mfice mafintafined fin SPF ffacfilfitfies. Treatment off mfice fin the CV ffacfilfity wfith antfibfiotfics abrogated the
regulatory capacfity off B cells. Ffinally, we fidentfified transfitfional B cells fisolated ffrom CV ffacfilfitfies
as possessfing the regulatory ffunctfion. These findfings demonstrate that B cells, and fin partficular
transfitfional B cells, can promote prolongatfion off grafft survfival, a ffunctfion dependent on lficensfing by
gut mficrolora.