title: Splenic Long-Lived Plasma Cells Promote the Development of Follicular Helper T Cells during Autoimmune Responses.
abstract: Long-lived plasma cells (LLPCs) develop under the help of follicular helper T (Tfh) cells and reside mainly in the bone marrow. However, these cells are unusually abundant in the spleen of several autoimmune models including K/BxNsf mice, yet their pathogenic impact remains unknown. To investigate a previously unappreciated role of splenic LLPCs, we sorted splenic plasma cells (PCs) from K/BxNsf and K/BxN mice, corresponding to LLPCs and conventional short-lived PCs, respectively, and compared their phenotypes and ability to prime and induce the differentiation of naive CD4(+) T cells into effector cells in vitro and in vivo. We found that K/BxNsf PCs had lower levels of the Ag presentation machinery and costimulators than K/BxN PCs, and also a lower CD4(+) T cell priming capacity. Autoantigen-pulsed K/BxNsf PCs selectively polarized cognate CD4(+) T cells toward the expression of molecules necessary for Tfh development and function. As a result, the K/BxNsf PC-primed CD4(+) T cells were more effective in stimulating B cells to produce autoantigen-specific IgGs than K/BxN PCs or even dendritic cells. Adoptive transfer of K/BxNsf PCs, but not K/BxN PCs, to K/BxN mice increased numbers of Tfh cells in draining lymph nodes. These results propose that abnormal accumulation of LLPCs in the spleen of autoimmune models drives the differentiation of autoantigen-primed CD4(+) T cells to Tfh cells. This positive feedback loop between splenic LLPCs and Tfh cells may contribute to the persistence of humoral autoimmunity.
authors.affiliation: Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, College of Medicine, Hanyang University, Seoul 133-791, South Korea;
authors.forename: Eunkyeong
authors.initials: E
authors.lastname: Jang
authors.affiliation: Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, College of Medicine, Hanyang University, Seoul 133-791, South Korea;
authors.forename: Wang Sik
authors.initials: WS
authors.lastname: Cho
authors.affiliation: Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, College of Medicine, Hanyang University, Seoul 133-791, South Korea;
authors.forename: Yeon-Kyung
authors.initials: YK
authors.lastname: Oh
authors.affiliation: Research Institute of Medical Science, Catholic University of Korea, Seoul 137-701, South Korea; and.
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
authors.affiliation: Department of Microbiology, College of Medicine, Hanyang University, Seoul 133-791, South Korea.
authors.forename: Jung Mogg
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, College of Medicine, Hanyang University, Seoul 133-791, South Korea; jhyoun@hanyang.ac.kr paikdj@hanyang.ac.kr.
authors.forename: Doo-Jin
authors.initials: DJ
authors.lastname: Paik
authors.affiliation: Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, College of Medicine, Hanyang University, Seoul 133-791, South Korea; jhyoun@hanyang.ac.kr paikdj@hanyang.ac.kr.
authors.forename: Jeehee
authors.initials: J
authors.lastname: Youn
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D020411:Oligonucleotide Array Sequence Analysis; D010950:Plasma Cells / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*