Hai Qi’s group from Tsinghua University revealed the novel mechanism in germinal center dependent memory B cell formation
Source:Hai Qi
2017-09-15
On Aug 18th, 2017, Dr. Hai Qi’s group from the School of Medicine & Institute for Immunology, Tsinghua University, reported in the Nature Immunology magazine about a new mechanism in germinal center dependent memory B cell formation (Wang et al., Germinal-center development of memory B cells driven by IL-9 from follicular helper T cells. Nature Immunology, 2017 Aug 18(8):921-930).

Immune Memory is the ability to control and avoid disease by a faster and stronger response when body is infected by the same antigen again. Antibody produced by B cell is crucial for controlling infection, while memory B cell is one of the key players.“Germinal Center” is the most important resource for memory B cells. However, the mechanism for memory B cell formation and the regulation of their development and function remain unclear. Comparing the dividing GC B cell and non-dividing memory B cells, Qi’s group are aiming to seek the transition state during these two type of cells.

Using a reporter mice which could report the different cell cycle,they find and isolate the transitional cell, namely, GC-MP owning the surface markers from both GC B and memory B cell. Besides, they further identify the transcriptional similarity and functional potential of GC-MP to memory B cell.

Germinal Center in Reporter Mice
Red color representing the cells in non-dividing stage, while cyan color representing the cels in DNA synthetizing/dividing stage. Germinal center is shown as semicircle region, in which red color containing GC-MP.

With the high expression level of IL-9R in GC-MP, Qi’s group also find the significant role of IL-9, an intercellular signaling transduction molecule, in memory B cell formation. There are hardly any research studying the role of IL-9 in antibody immune response. By knock-out mice, antibody blocking and IL-9 administration, they reveal the IL-9 produced by Tfh cells is one of the key factors for GC-MP formation and their differentiation to memory B cell.

Qi’s work first describes a panorama for memory B cell formation from germinal centers. Not only the critical GC-MP but also the first cytokines—IL-9 produced by T cells are found. Therefore, this work discovers a key clue to solve the mysteries in memory B cell formation as well as providing new ways for future immune therapy and antibody design.

Dr. Xuerui Yang’s group from the School of Life Sciences, Tsinghua University and Dr. Lianfeng Zhang’s group from Union Medical college contribute to this project. This research is supported by grants from the Natural Science Foundation of China and Ministry of Science and Technology of China (973 Program),the Key Project of Natural Science Foundation of China, National Outstanding Youth Funds and Innovative group project, as well as Tsinghua-Peking University Center for Life Sciences.

Link:http://www.nature.com/doifinder/10.1038/ni.3788