Splenic Long-Lived Plasma Cells Promote the Development of Follicular Helper T Cells during Autoimmune Responsesopen access
- Authors
- Jang, Eunkyeong; Cho, Wang Sik; Oh, Yeon-Kyung; Cho, Mi-La; Kim, Jung Mogg; Paik, Doo-Jin; Youn, Jeehee
- Issue Date
- Feb-2016
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Citation
- JOURNAL OF IMMUNOLOGY, v.196, no.3, pp.1026 - 1035
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Volume
- 196
- Number
- 3
- Start Page
- 1026
- End Page
- 1035
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/155166
- DOI
- 10.4049/jimmunol.1401059
- ISSN
- 0022-1767
- 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.
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