title: Cutting Edge: CTLA-4Ig Inhibits Memory B Cell Responses and Promotes Allograft Survival in Sensitized Recipients.
abstract: Sensitized recipients with pretransplant donor-specific Abs are at higher risk for Ab-mediated rejection than nonsensitized recipients, yet little is known about the properties of memory B cells that are central to the recall alloantibody responses. Using cell enrichment and MHC class I tetramers, C57BL/6 mice sensitized with BALB/c splenocytes were shown to harbor H-2K(d)-specific IgG(+) memory B cells with a post-germinal center phenotype (CD73(+)CD273(+)CD38(hi)CD138(-)GL7(-)). These memory B cells adoptively transferred into naive mice without memory T cells recapitulated class-switched recall alloantibody responses. During recall, memory H-2K(d)-specific B cells preferentially differentiated into Ab-secreting cells, whereas in the primary response, H-2K(d)-specific B cells differentiated into germinal center cells. Finally, our studies revealed that, despite fundamental differences in alloreactive B cell fates in sensitized versus naive recipients, CTLA-4Ig was unexpectedly effective at constraining B cell responses and heart allograft rejection in sensitized recipients.
authors.affiliation: Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, IL 60637.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, IL 60637.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, IL 60637.
authors.forename: Dengping
authors.initials: D
authors.lastname: Yin
authors.affiliation: Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, IL 60637.
authors.forename: Vinh
authors.initials: V
authors.lastname: Vu
authors.affiliation: Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, IL 60637.
authors.forename: Roger
authors.initials: R
authors.lastname: Sciammas
authors.affiliation: Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, IL 60637 achong@uchicago.edu.
authors.forename: Anita S
authors.identifier: http://orcid.org/0000-0003-0460-0196
authors.initials: AS
authors.lastname: Chong
mesh_terms: D015720:5'-Nucleotidase / Q000032:analysis; D000069594:Abatacept / Q000494:pharmacology*; D064591:Allografts; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D006085:Graft Survival; D016027:Heart Transplantation; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000032:analysis
chemical_list: D061027:Programmed Cell Death 1 Ligand 2 Protein; D000069594:Abatacept; D015720:5'-Nucleotidase