The immune system produces antibodies finely tuned to antigens. Recent research describes how the interaction between T cells (green) and B cells (blue) allows this to take place. Bystander B cells and antigen appear in red.
Credit: Laboratory of Molecular Immunology at The Rockefeller University
Cell Division speeds up as part of antibody selection. Mechanisms that favor selection of B cells capable of producing antibodies with highest affinity for that invader. “2 of the mechanisms that allow high affinity B cells to overwhelm the others,” says Alex Gitlin.
During an infection, B + other immune cells form germinal centers in spleen and lymph nodes, where B cells evolve in a Darwinian-like fashion. The gene responsible for producing their antibodies mutates rapidly, a million times faster than normal rate of mutation, and cells proliferate. B cells whose mutations increase Ag’s affinity for Ag’s are selected, and these cells then continue to mutate and proliferate. “Previously, we showed that high affinity cells spend more time dividing and mutating in between rounds of competition. We now show that these high affinity cells also use this additional time more effectively – by dividing at faster rates”.
As vaccines depend on effective antibody responses for protection, a better understanding of the antibody selection process in the germinal center might potentially be of use for developing more effective vaccines.
Within germinal cells, B cells travel between dark zone and light zone. In the dark zone, the B cells mutate and proliferate, before traveling to the light zone, where they pick up pieces of antigen. The higher the affinity of their antibodies, the more antigen they pick up. Their previous experiments demonstrated the T cell, operates in the light zone to recognize the higher affinity B cells based on the amount of antigen they display. The more antigen the B cells present to T cells, the stronger the signal the T cells send. Thus, high affinity B cells spend more time in the dark zone in between visits to the light zone.
>>Reason 2 for high affinity selection: more rapid cell divisions. Through mouse expts, they found a T cell signal prompts high affinity B cells to divide more rapidly while in the dark zone. ie cells have more time and speed to duplicate themselves. By labeling DNA replication and following its progression, the team saw how S phase of the cell cycle, in which the cell copies its DNA in prep for division, is sped up. Acceleration during this phase was due to dsDNA molecule being unzipped and copied more rapidly at the replication fork.
“Together, these studies describe 2 complementary ways in which signals from T cells empower the best equipped set of B cells to take over the immune response during affinity maturation. Other mechanisms, which are yet to be discovered, are also likely to be at play,” Gitlin says…”they may also have important implications for improving vaccines and understanding lymphomas, which often arise from germinal center” http://newswire.rockefeller.edu/2015/07/16/cell-division-speeds-up-as-part-of-antibody-selection-study-shows/
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