title: Antibodies from donor B cells perpetuate cutaneous chronic graft-versus-host disease in mice.
abstract: Cutaneous sclerosis is one of the most common clinical manifestations of chronic graft-versus-host disease (cGVHD). Donor CD4(+) T and B cells play important roles in cGVHD pathogenesis, but the role of antibodies from donor B cells remains unclear. In the current studies, we generated immunoglobulin (Ig)H(µγ1) DBA/2 mice whose B cells have normal antigen-presentation and regulatory functions but cannot secrete antibodies. With a murine cGVHD model using DBA/2 donors and BALB/c recipients, we have shown that wild-type (WT) grafts induce persistent cGVHD with damage in the thymus, peripheral lymphoid organs, and skin, as well as cutaneous T helper 17 cell (Th17) infiltration. In contrast, IgH(µγ1) grafts induced only transient cGVHD with little damage in the thymus or peripheral lymph organs or with little cutaneous Th17 infiltration. Injections of IgG-containing sera from cGVHD recipients given WT grafts but not IgG-deficient sera from recipients given IgH(µγ1) grafts led to deposition of IgG in the thymus and skin, with resulting damage in the thymus and peripheral lymph organs, cutaneous Th17 infiltration, and perpetuation of cGVHD in recipients given IgH(µγ1) grafts. These results indicate that donor B-cell antibodies augment cutaneous cGVHD in part by damaging the thymus and increasing tissue infiltration of pathogenic Th17 cells.
authors.affiliation: Departments of Diabetes Research and Hematology/Hematopoietic Cell Transplantation, The Beckman Research Institute of City-Hope, Duarte, CA; Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China;
authors.forename: Hua
authors.initials: H
authors.lastname: Jin
authors.affiliation: Departments of Diabetes Research and Hematology/Hematopoietic Cell Transplantation, The Beckman Research Institute of City-Hope, Duarte, CA; Department of Hematology, Changhai Hospital, The Second Military Medical University, Shanghai, China;
authors.forename: Xiong
authors.initials: X
authors.lastname: Ni
authors.affiliation: Departments of Diabetes Research and Hematology/Hematopoietic Cell Transplantation, The Beckman Research Institute of City-Hope, Duarte, CA;
authors.forename: Ruishu
authors.initials: R
authors.lastname: Deng
authors.affiliation: Departments of Diabetes Research and Hematology/Hematopoietic Cell Transplantation, The Beckman Research Institute of City-Hope, Duarte, CA; Department of Hematology, Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou, China;
authors.forename: Qingxiao
authors.initials: Q
authors.lastname: Song
authors.affiliation: Departments of Diabetes Research and Hematology/Hematopoietic Cell Transplantation, The Beckman Research Institute of City-Hope, Duarte, CA; Irell and Manella Graduate School of Biological Sciences-City of Hope, Duarte, CA; and.
authors.forename: James
authors.initials: J
authors.lastname: Young
authors.affiliation: Departments of Diabetes Research and Hematology/Hematopoietic Cell Transplantation, The Beckman Research Institute of City-Hope, Duarte, CA; Irell and Manella Graduate School of Biological Sciences-City of Hope, Duarte, CA; and.
authors.forename: Kaniel
authors.initials: K
authors.lastname: Cassady
authors.affiliation: Departments of Diabetes Research and Hematology/Hematopoietic Cell Transplantation, The Beckman Research Institute of City-Hope, Duarte, CA;
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Departments of Diabetes Research and Hematology/Hematopoietic Cell Transplantation, The Beckman Research Institute of City-Hope, Duarte, CA; Irell and Manella Graduate School of Biological Sciences-City of Hope, Duarte, CA; and.
authors.forename: Stephen
authors.initials: S
authors.lastname: Forman
authors.affiliation: Divisions of Clinical Research and Medical Oncology, Fred Hutchinson Cancer Research Center/University of Washington, Seattle, WA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China;
authors.forename: Qifa
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Departments of Diabetes Research and Hematology/Hematopoietic Cell Transplantation, The Beckman Research Institute of City-Hope, Duarte, CA; Irell and Manella Graduate School of Biological Sciences-City of Hope, Duarte, CA; and.
authors.forename: Defu
authors.identifier: 0000-0001-9585-1411
authors.initials: D
authors.lastname: Zeng
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D054418:Chemokine CCL20 / Q000378:metabolism; D002908:Chronic Disease; D003713:Dendritic Cells / Q000378:metabolism; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D007074:Immunoglobulin G / Q000032:analysis; D007143:Immunoglobulin Heavy Chains; D007142:Immunoglobulin gamma-Chains / Q000235:genetics / Q000276:immunology; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000276:immunology; D053759:Interleukin-23 / Q000378:metabolism; D007518:Isoantibodies / Q000276:immunology*; D008221:Lymphoid Tissue / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D011828:Radiation Chimera; D012867:Skin / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D058504:Th17 Cells / Q000276:immunology; D013950:Thymus Gland / Q000473:pathology
chemical_list: C493447:CCL20 protein, mouse; D054418:Chemokine CCL20; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007142:Immunoglobulin gamma-Chains; D007148:Immunoglobulin mu-Chains; D053759:Interleukin-23; D007518:Isoantibodies