Antibodies are Y-shaped proteins that are made by the immune system to identify and neutralize pathogens. The generation of good antibodies during an immune response is essential for the body to protect itself against pathogens. Moreover, the vast majority of all vaccines are based on the formation of antibodies.

During an immune response the cells that produce antibodies (B cells) undergo selection, during which the cells producing the best antibodies are selected and induced to multiply. “This allows us to make and select “sharpshooters” – B cells that make antibodies that bind really tightly to pathogens”, explains Shiv Pillai a professor of Medicine at the Harvard Medical School. This process occurs in specialized structures called germinal centers. Previously, scientists assumed that one germinal center harbors one B cell variant that mutates and is selected within this germinal center.

In a study published this month in the journal “Science”, Tas and colleagues were able to monitor in an extremely elegant fashion the antibody selection by combining microscopy and sequencing. The authors made use of a system allowing individual B cells to be uniquely colored with fluorescent proteins (see picture). The results of the analysis were astounding. The researchers found some germinal centers to become mono-colored whereas others consisted of many different colors (see picture), indicating that many B cells can coexist and be selected in the same germinal center. These results imply that the immune system does not make one definite dominant antibody, but rather develops many different coexisting antibodies.

“We hope that in the future a better understanding of the factors that drive B cell selection in germinal centers will aid us in developing vaccines for yet untreatable infections”, explicates Jeroen Tas the first author of the study and a PhD student in the Harvard Immunology program.

Acknowledgments: Many thanks to Professor Shiv Pillai, Professor of Medicine at the Harvard Medical School, and Jeroen Tas, PhD student in Immunology at the Harvard Medical School for helpful discussions, comments and providing the picture.

Tas, Jeroen MJ, et al. “Visualizing antibody affinity maturation in germinal centers.” Science 351.6277 (2016): 1048-1054. Link: http://science.sciencemag.org/content/351/6277/1048

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