Characterizing the B-Cell and Humoral Response in Tertiary Lymphoid Organs in Kidney Allografts. 2019

Anna K Nowocin, and Lucy Meader, and Kathryn Brown, and Raul Elgueta, and Wilson Wong
From the MRC Centre for Transplantation, King's College London School of Medicine at Guy's, King's and St. Thomas' Hospitals, London, United Kingdom.

Tertiary lymphoid organs are formed at sites of chronic inflammation and are thought to contribute to the immune response. Here, we aimed to characterize the structure and function of tertiary lymphoid organs in a model of murine kidney allotransplant to understand their role in alloimmunity. We transplanted 4 C57BL/6 mouse kidneys (isograft group) and 17 DBA/2 mouse kidneys into C57BL/6 mouse recipients. Three DBA/2-to-C57BL/6 transplant mice that rejected their grafts acutely (before 10 days posttransplant) were excluded from the study. The 14 surviving DAB2 grafts were retrieved at day 45 posttransplant and evaluated histologically. The presence of antibody-secreting cells and circulating levels of donor-specific antibodies were also evaluated. We found that tertiary lymphoid organs can be associated with a beneficial response in a kidney allotransplant model. Characterization of B-cell subsets within tertiary lymphoid organs in mouse kidney allografts revealed naive, plasma, and memory B cells, which were mostly grouped within or in close proximity of tertiary lymphoid organs. Staining for intracellular immunoglobulin G showed that many of the B cells within tertiary lymphoid organs were capable of producing antibodies. Although allospecific antibodies were found in the serum of recipient mice and were deposited in the transplanted kidneys, graft function was not affected in this model. B cells within tertiary lymphoid organs are functional and contribute to the humoral arm of the alloresponse. However, tertiary lymphoid organs are not necessarily associated with graft rejection, suggesting that protective mechanisms are at play.

UI MeSH Term Description Entries
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008811 Mice, Inbred DBA An inbred strain of mouse. Specific substrains are used in a variety of areas of BIOMEDICAL RESEARCH such as DBA/1J, which is used as a model for RHEUMATOID ARTHRITIS. Mice, DBA,Mouse, DBA,Mouse, Inbred DBA,DBA Mice,DBA Mice, Inbred,DBA Mouse,DBA Mouse, Inbred,Inbred DBA Mice,Inbred DBA Mouse
D000072717 Tertiary Lymphoid Structures Aggregates of immune cells formed near the sites of chronically inflamed, infected, or tumorous tissues. Ectopic Lymph Nodes,Ectopic Lymphoid Follicles,Ectopic Lymphoid Formations,Ectopic Lymphoid Organs,Ectopic Lymphoid Tissues,Ectopic Lymphoid-Like Structures,Ectopic Lymph Node,Ectopic Lymphoid Follicle,Ectopic Lymphoid Formation,Ectopic Lymphoid Like Structures,Ectopic Lymphoid Organ,Ectopic Lymphoid Tissue,Ectopic Lymphoid-Like Structure,Lymph Node, Ectopic,Lymph Nodes, Ectopic,Lymphoid Follicle, Ectopic,Lymphoid Follicles, Ectopic,Lymphoid Formation, Ectopic,Lymphoid Formations, Ectopic,Lymphoid Organ, Ectopic,Lymphoid Organs, Ectopic,Lymphoid Structure, Tertiary,Lymphoid Structures, Tertiary,Lymphoid Tissue, Ectopic,Lymphoid Tissues, Ectopic,Lymphoid-Like Structure, Ectopic,Lymphoid-Like Structures, Ectopic,Tertiary Lymphoid Structure
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001402 B-Lymphocytes Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent
D016030 Kidney Transplantation The transference of a kidney from one human or animal to another. Grafting, Kidney,Renal Transplantation,Transplantation, Kidney,Transplantation, Renal,Kidney Grafting,Kidney Transplantations,Renal Transplantations,Transplantations, Kidney,Transplantations, Renal
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D056724 Immunity, Humoral Antibody-mediated immune response. Humoral immunity is brought about by ANTIBODY FORMATION, resulting from TH2 CELLS activating B-LYMPHOCYTES, followed by COMPLEMENT ACTIVATION. Humoral Immune Response,Humoral Immune Responses,Humoral Immunity,Immune Response, Humoral,Immune Responses, Humoral,Response, Humoral Immune
D064591 Allografts Tissues, cells, or organs transplanted between genetically different individuals of the same species. Allogeneic Grafts,Allogeneic Transplants,Homografts,Homologous Transplants,Allogeneic Graft,Allogeneic Transplant,Allograft,Graft, Allogeneic,Grafts, Allogeneic,Homograft,Homologous Transplant,Transplant, Allogeneic,Transplant, Homologous,Transplants, Allogeneic,Transplants, Homologous

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