homeostatic regulation of marginal zone b cells by invariant natural killer t cells边缘区b细胞的稳态调节不变的自然杀伤t细胞.pdfVIP

Homeostatic Regulation of Marginal Zone B Cells by Invariant Natural Killer T Cells 1. 2,3. 1 1,4,5 Xiangshu Wen , Jun-Qi Yang , Peter J. Kim , Ram Raj Singh * 1 Autoimmunity and Tolerance Laboratory, Division of Rheumatology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America, 2 University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America, 3 Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu, China, 4 Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, United States of America, 5 Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California, United States of America Abstract ¨ Marginal zone B cells (MZB) mount a rapid antibody response, potently activate naıve T cells, and are enriched in autoreactive B cells. MZBs express high levels of CD1d, the restriction element for invariant natural killer T cells (iNKT). Here, we examined the effect of iNKT cells on MZB cell activation and numbers in vitro and in vivo in normal and autoimmune mice. Results show that iNKT cells activate MZBs, but restrict their numbers in vitro and in vivo in normal BALB/c and C57/BL6 mice. iNKT cells do so by increasing the activation-induced cell death and curtailing proliferation of MZB cells, whereas they promote the proliferation of follicular B cells. Sorted iNKT cells can directly execute this function, without help from other immune cells. Such MZB regulation by iNKTs is mediated, at least in part, via CD1d on B c