title: Tracing Donor-MHC Class II Reactive B cells in Mouse Cardiac Transplantation: Delayed CTLA4-Ig Treatment Prevents Memory Alloreactive B-Cell Generation.
abstract: The dual role of B cells as drivers and suppressors of the immune responses have underscored the need to trace the fate of B cells recognizing donor major histocompatibility complex class I and class II after allograft transplantation.
  
  
  
  In this study, we used donor class II tetramers to trace the fate of I-E-specific B cells after immunization with BALB/c spleen cells or cardiac transplantation, in naive or sensitized C57BL/6 recipients. We combined this approach with genetic lineage tracing of memory B cells in activation-induced cytidine deaminase regulated Cre transgenic mice crossed to the ROSA26-enhanced yellow fluorescent protein reporter mice to track endogenous I-E-specific memory B cell generation.
  
  
  
  Immunization with BALB/c splenocytes or heart transplantation induced an expansion and differentiation of I-E-specific B cells into germinal center B cells, whereas BALB/c heart transplantation into sensitized recipients induced the preferential differentiation into antibody-secreting cells. A 10.8-fold increase in the frequency of I-E-specific memory B cells was observed by day 42 postimmunization. Treatment with CTLA4-Ig starting on day 0 or day 7 postimmunization abrogated I-E-specific memory B cell generation and sensitized humoral responses, but not if treatment commenced on day 14.
  
  
  
  The majority of donor-specific memory B cells are generated between days 7 and 14 postimmunization, thus revealing a flexible timeframe whereby delayed CTLA4-Ig administration can inhibit sensitization and the generation of memory graft-reactive B cells.
authors.affiliation: 1 Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, IL.2 Department of Organ Transplantation, Shanghai ChangZheng Hospital, Second Military Medical University, Shanghai, China.3 Center for Immunobiology and Transplant Research, Department of Surgery, The Houston Methodist Hospital Research Institute, Houston, TX.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Yang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chen
authors.forename: James S
authors.initials: JS
authors.lastname: Young
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Dengping
authors.initials: D
authors.lastname: Yin
authors.forename: Roger
authors.initials: R
authors.lastname: Sciammas
authors.forename: Anita S
authors.initials: AS
authors.lastname: Chong
mesh_terms: D000069594:Abatacept / Q000008:administration & dosage*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D019070:Cell Lineage; D049109:Cell Proliferation / Q000187:drug effects*; D058948:Cell Tracking / Q000379:methods; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005838:Genotype; D006084:Graft Rejection / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation / Q000009:adverse effects*; D000949:Histocompatibility Antigens Class II / Q000097:blood / Q000276:immunology*; D007156:Immunologic Memory; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D019426:Integrases / Q000235:genetics; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D022661:RNA, Untranslated / Q000235:genetics; D013997:Time Factors
chemical_list: D001426:Bacterial Proteins; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D008164:Luminescent Proteins; D022661:RNA, Untranslated; C054562:yellow fluorescent protein, Bacteria; D000069594:Abatacept; C045073:Cre recombinase; D019426:Integrases; D003564:Cytidine Deaminase