title: Anti-CD3ε induces splenic B220lo B-cell expansion following anti-CD20 treatment in a mouse model of allosensitization.
abstract: Antibodies targeting T cells and B cells are increasingly used for immunosuppression in clinical transplantation. However, the impact of T-cell depletion by antibodies on B-cell homeostasis is poorly understood. Using a mouse model of allosensitization with skin allograft, we investigated whether targeting T cells by anti-CD3ε alters peripheral B-cell homeostasis and alloantibody responses following B-cell depletion by anti-CD20. We found that anti-CD3ε induced a discrete B220(lo), but not a conventional B220(hi) subset, in the spleens of the allosensitized mice 14 days after anti-CD20 treatment. The splenic B220(lo) cells were refractory to anti-CD20 depletion. Flow cytometry revealed that the splenic B220(lo) cells were phenotypically similar to the B220(lo) AA4.1(+) CD23(-) sIgM(lo) sIgD(-) developing B cells (pre-B to immature B) normally presented in the bone marrow. Despite the presence of the splenic B220(lo) cells, mice treated with combined anti-CD3ε/CD20 produced limited alloantibodies in response to the primary skin allografts. Alloantibody production increased significantly in the mice following re-immunization by donor-specific splenocytes. We conclude that anti-CD3ε can induce an expansion of B220(lo) B cells in the spleens after B-cell depletion by anti-CD20. These B cells are not producing alloantibodies, but re-immunization of the mice with alloantigen leads to risk of alloantibody response.
authors.affiliation: Comprehensive Transplant Center and Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Todo
authors.forename: Gordon
authors.initials: G
authors.lastname: Wu
authors.forename: Ning-ning
authors.initials: NN
authors.lastname: Chai
authors.forename: Yao
authors.initials: Y
authors.lastname: He
authors.forename: Gislaine
authors.initials: G
authors.lastname: Martins
authors.forename: Ankur
authors.initials: A
authors.lastname: Gupta
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Fair
authors.forename: Nai-you
authors.initials: NY
authors.lastname: Liu
authors.forename: Stanley
authors.initials: S
authors.lastname: Jordan
authors.forename: Andrew
authors.initials: A
authors.lastname: Klein
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018951:Antigens, CD20 / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002469:Cell Separation; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006706:Homeostasis / Q000187:drug effects / Q000276:immunology; D007165:Immunosuppression Therapy / Q000379:methods; D007518:Isoantibodies / Q000096:biosynthesis / Q000276:immunology; D008212:Lymphocyte Depletion / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D060888:Real-Time Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D017252:CD3 Complex; D007518:Isoantibodies