Poster Board I-364
Chronic graft versus host disease (GVHD) is an autoimmune-like disease, in which both donor CD4+ T and B cells play important roles in the pathogenesis. However, it is unclear how donor CD4+ T and B cells interact in the context of chronic GVHD. In our current studies, we found that, in a new chronic GVHD model of MHC-matched DBA/2 donor to BALB/c host, depletion of donor CD4+ T cells in transplants prevented donor B220+ B cell upregulation of co-stimulatory molecules (i.e. B7.1, B7.2, and MHC II), prevented donor B cell differentiation into syndecan+ IgG anti-dsDNA autoantibody-producing plasma cells, and prevented the induction of chronic GVHD. In addition, we found that donor CD4+ T cells were able to drive both marginal zone B (AA4.1−B220+CD1dhiCD23lo) and follicular B (AA4.1−B220+CD23hiCD1dlo) cells to become IgG autoantibody-producing cells. On the other hand, depletion of donor B220+ B cells in transplants prevented expansion of donor-type CD4+ T cells that proliferated in response to donor DC stimulation, prevented the skewing of TCR CDR3-length of the donor CD4+ T cells as revealed by TCR spectratyping, and prevented induction of chronic GVHD. These results indicate that donor CD4+ T and B cells mutually activate each other in the chronic GVHD recipients; alloreactive donor CD4+ T cells activate and drive donor B cell differentiation into IgG autoantibody producing cells, in turn, donor B cells mediate the expansion and TCR-spreading of autoreactive donor CD4+ T cells. Therefore, donor CD4+ T and B cells in transplants orchestrate the development of chronic GVHD. This work is supported by NIH R01 AI066008.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.