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Invasive cancer cells marked by distinctive mutations

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immunogloblulins

Antibody diversity mutations come from a vast genetic library

Vaccine scientists want to nudge the immune system into producing antibodies that will protect us from infection. In doing so, they are playing with fire – in a limited way. With every healthy antibody response, a process of internal evolution takes place among B cells, the immune cells that produce antibodies. It’s called “somatic hypermutation.”

In the lymph nodes, individual B cells undergo an accelerated rate of mutation. It’s as if those B cells’ DNA were being cooked with radiation or mutagenic chemicals – but only in a few genes. Then the lymph nodes select the B cells with high-affinity antibodies.

Gordon Dale, a just-defended graduate student from Joshy Jacob’s lab in Emory Vaccine Center, has a new paper in Journal of Immunology that sheds light on how somatic hypermutation takes place in both mice and humans.

In particular, Dale and Jacob found that the mutations that occur in human and mouse antibody genes are not random. They appear to borrow information from gene segments that are leftovers from the process of assembling antibody DNA in B cells.

In a mix and match process called VDJ recombination, B cells use one of many V, D, and J segments to form their antibody genes. What Dale and Jacob were looking at occurs after the VDJ step, when B cells get stimulated as part of an immune response.

They analyzed the patterns of mutations in human and mouse antibody genes, and found that mutations tend to come together, in a way that suggests that they are being copied from leftover V segments. They call this pattern “tem Read more

Posted on by Quinn Eastman in Immunology Leave a comment