Project Summary/Abstract Core C Chronic graft-versus-host disease (cGVHD) is the leading cause of late morbidity, impaired quality of life, and mortality after allogeneic hematopoietic cell transplantation (HCT). Despite this, little progress has been made in cGVHD prevention and therapy in part because the pathophysiology of cGVHD is poorly understood. The pathophysiology of cGVHD is distinct from acute GVHD, and B cells are implicated. The primary objective of research projects in this Program Project application is thus to study the role of the B cell in the pathophysiology of cGVHD. Specifically, Project 1 is dedicated to clinical trials that specifically target the B cell compartment for the prevention and treatment of cGVHD. Project 2 will examine novel drugs that target germinal centers, plasma cells, and immune recognition of collagen using an established robust mouse model of cGVHD. Project 3 will examine B cell responses to H-Y antigens using samples from clinical trials, correlate B cell depletion and serologic alloantibody depletion with clinical responses, perform novel alloantigen discovery studies, and study the biology of alloreactive B cells to determine signaling pathways that can be therapeutically targeted in cGVHD. The primary objective of the Biostatistics Core (Core C) is to provide statistical collaboration for all investigators involved in this Program Project. This includes collaboration with project investigators in the design of clinical trials in Project 1 and laboratory experiments in Projects 2 and 3, analysis of clinical and laboratory data and to establish correlations of clinical outcomes with laboratory results in Projects 1-3, and participate in manuscript writing in all Projects. Core C will also provide research infrastructure for translational research in all projects and computing resources. These services will be executed under the direction of Dr. Kim, Core C Leader, and will be carried out in 4 Specific Aims: 1) To provide biostatistical collaboration for translational clinical research studies. 2) To provide biostatistical collaboration for translational animal research studies. 3) To provide biostatistical collaboration for translational laboratory research studies. 3) To provide research infrastructure for translational research and computing resources for data processing, and statistical analysis, standardized reporting, and quality control.