Chemical Attraction Prompts B Cell Migration

Scientists from the University of California, San Francisco (UCSF, USA) have found that chemical attraction is the key to understanding how B cells that make antibodies find the T cells they must team up with to attack invading pathogens. The research, based on studies of mice, is published in the March 7, 2002 issue of the journal Nature.

Prior to encountering foreign antigens, B cells concentrate in regions within the lymphatic system where few T cells reside (the B zone), anchored by their attraction to a type of chemical attractant, or chemokine called CXCL13. Contact with an antigen from an invading microbe triggers changes in the B cell surface resulting in the doubling of receptors on its surface cued to a different group of chemokines known as CCL19 and CCL21. These are found in far greater concentration where T cells reside (the T zone). The increased receptiveness to these signals prompts the B cells to migrate within the lymphatic tissue from the B zone to the boundary between the B and T zones where cells of the two types can pair up. The pairing is known to be essential for the immune system to mount an antibody attack.

In experiments with mice and mice cells, the researchers used a gene therapy approach to show that artificially increasing the numbers of receptors for T zone chemokines, CCL19 and CCL21, on B cells was sufficient to cause B cell migration to the T zone. Reciprocally, B cells with artificially increased receptors for the CXCL13 chemokine, overcame the attractive signals from the T zone and retreated to the B zone.

Using B cells from mice with mutations in the receptor for the T zone chemokines, the researchers showed that this receptor was essential for the re-routing behavior. B cells with increased receptors for T zone chemokines (CCL19 and CCL21) but no receptors for the B zone chemokine CXCL13 no longer took the route that ran along the boundary of the two neighborhoods, but instead headed directly toward the T zone.

The findings led to the conclusion that B cell migration is at least partially determined by the balance of responsiveness to the two kinds of chemical attractants made in adjacent zones with the B cells becoming much more responsive to being pulled toward the T zone after they are exposed to an antigen.

"We have known for some time that the antigen triggers a change that prompts B cell migration, but we did not know how the process worked,” said Jason Cyster, Ph.D., a UCSF associate professor of microbiology and immunology.

The researchers now hope to determine whether similar changes in chemokine receptor levels are involved in redirecting the movement of autoreactive B cells. If this proves to be true, they think they may be on the path to resolving what goes wrong in some people to cause autoantibody-mediated disease. Blocking these attractants may prove an effective strategy to block autoantibody mediated disease.




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