2015年
A subset of AID-dependent B-1a cells initiates hypersensitivity and pneumococcal pneumonia resistance
B-1 CELL DEVELOPMENT AND FUNCTION
- 巻
- 1362
- 号
- 1
- 開始ページ
- 200
- 終了ページ
- 214
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1111/nyas.12975
- 出版者・発行元
- BLACKWELL SCIENCE PUBL
We propose that there is a special B-1a B cell subset ("sB-1a" cells) that mediates linked processes very early after immunization to initiate cutaneous contact sensitivity (CS), delayed-type hypersensitivity (DTH), and immune resistance to pneumococcal pneumonia. Our published data indicate that in CS and DTH, these initiating processes are required for elicitation of the delayed onset and late-occurring classical T cell-mediated responses. sB-1a cells resemble memory B2 cells, as they are stimulated within 1 h of immunization and depend on T helper cytokines-uniquely IL-4 from hepatic iNKT cells-for activation and rapid migration from the peritoneal cavity to the spleen to secrete IgM antibody (Ab) and Ab-derived free light chains (FLCs) by only 1 day after immunization. Unlike conventional B-1a (cB-1a) cell-produced IgM natural Ab, IgMAb produced by sB-1a cells has high Ag affinity owing to immunoglobulin V-region mutations induced by activation-induced cytidine deaminase (AID). The dominant cB-1a cells are increased in immunized AID-deficient mice but do not mediate initiation, CS, or pneumonia resistance because natural Ab has relatively low Ag affinity because of unmutated germ-line V regions. In CS and DTH, sB-1a IgM Ag affinity is sufficiently high to mediate complement activation for generation of C5a that, together with vasoactive mediators such as TNF-alpha released by FLC-sensitized mast cells, activate local endothelium for extravascular recruitment of effector T cells. We conclude by discussing the possibility of functional sB-1 cells in humans.
- リンク情報
-
- DOI
- https://doi.org/10.1111/nyas.12975
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/26662721
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681304
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000366286200023&DestApp=WOS_CPL
- 共同研究・競争的資金等の研究課題
- インターロイキン IL-13 と B-1 細胞による急性感染症予後制御機構
- 共同研究・競争的資金等の研究課題
- iNKT細胞とB-1B細胞移入による重症型急性肺炎治療の研究
- ID情報
-
- DOI : 10.1111/nyas.12975
- ISSN : 0077-8923
- PubMed ID : 26662721
- PubMed Central 記事ID : PMC4681304
- Web of Science ID : WOS:000366286200023