Intrinsic MyD88-activation in B cells is necessary for development of alloreactive memory T cells (TRAN3P.902)

Abstract

Abstract B cells help alloreactive T cells to differentiate into memory T cells. Since B cells express TLRs, we asked whether MyD88-mediated activation of B cells is required for T cell activation and differentiation to memory T cells. Methods: Irradiated μMTCD45.1 mice were transplanted with bone marrow cells from μMTCD45.1 and wtCD45.2 (μMT+wt) or μMTCD45.1 and MyD88-/-CD45.2 (μMT+MyD88-/-). Differences in congenic background allowed us to confirm that following reconstitution, MyD88 deficiency was essentially restricted to B cells. μMT+MyD88-/- and μMT+wt received Balb/c skin transplants. Results: Rejection of allografts was comparable between μMT+MyD88-/- and μMT+wt chimeras (MST=18 days). μMT+MyD88-/- recipients showed 3-fold more alloreactive IFNγ+ CD4 and CD8 effector T cells when compared to μMT+wt mice at day 14 (p<0.05). IL-10+ B cells were diminished (p<0.005) in μMT+MyD88-/- than in μMT+wt chimeras. CD8 memory precursor T cells (CD44hi CD62Llo CD127hi) in μMT+MyD88-/- showed predominantly Bcl2lo expression in both KLRG1lo memory precursor effector cell (MPEC) and KLRG1hi short-lived effector cell (SLEC) populations. Consistent with these findings, fewer alloreactive CD4 and CD8 IFNγ+ memory T cells were seen in μMT+MyD88-/- (p<0.005) resulting in impaired memory recall (MST = 27 vs. 15 days, p < 0.005) than in μMT+wt chimeras. Conclusions: Intrinsic MyD88-dependent B cell functions are important for alloreactive T cell differentiation into long-lived memory T cells.