Scientists from the Garvan Institute of Medical Research in Australia say they have discovered an additional role for antibody-making B cells. The finding by Stacey Walters, senior research assistant, and Shane Grey, Ph.D., associate professor, shows that B cells also participate in the development of regulatory T cells.
Their study (“A Role for Intrathymic B Cells in the Generation of Natural Regulatory T Cells”) appears in the Journal of Immunology.
T cells develop in the thymus gland and from a naïve or undifferentiated state they are gradually “educated” to become helpers, or warriors, or regulators. Until now, the only nonthymic cells known to educate the regulators were dendritic cells, which travel to the thymus to deliver antigens. Now we know B cells can do the same thing, according to the Garvan group.
B cells have been thought to specialize only in the production of antibodies. As newfound educators of T cells as well, B cells become much more interesting and complex characters, potentially useful in helping to prevent organ rejection, control inflammatory bowel disease, or quell autoimmune conditions, noted Dr. Grey. That is because regulatory T cells control how killer T cells behave—and can effectively prevent the warriors from attacking “self” tissue, or tissue perceived as foreign. In the case of organ transplantation, several studies have shown that high levels of regulatory T cells can prevent organ rejection.
“Regulatory T cells are critical in the outcome of an immune response, so anything that in turn regulates them becomes very interesting to immunologists,” added Dr. Grey. “Right now there are clinical trials around the world looking to expand populations of these cells in patients. Researchers are also working on ways to grow regulatory cells in the laboratory to infuse into patients as therapy.”
Everyone is interested in finding ways to treat autoimmunity and prevent transplant rejection, he continued. “Expansion of regulatory T cells should help in both cases. Our finding suggests it should be possible to set up systems that harness B cells to expand regulatory cells.”
The Garvan lab members worked with mice genetically modified to express high levels of “BAFF”, a substance that increases survival of B cells. The higher number of B cells overall allowed researchers to track the activity of B cells in the thymus.
“Thymic Treg [regulatory T-cell] development was diminished in both B cell–deficient BAFF-Tg chimeras, but also B cell–deficient wild-type chimeras,” wrote the investigators. “B cell Ag capture and presentation are critical in vivo events for Treg development. In the absence of B cell surface MHC class II expression, thymic expansion of BAFF-Tg Tregs was lost. Further to this, expansion of Tregs did not occur in BAFF-Tg/Ig hen egg lysozyme BCR chimeras, demonstrating a requirement for Ag specificity. Thus, we present a mechanism whereby intrathymic B cells, through the provision of cognate help, contribute to the shaping of the Treg repertoire.
“It has been known for years that some B cells travel to the thymus, but no one has understood why,” said Walters. “Our experiments showed clearly that B cells participated in the creation of regulatory T cells. The more B cells that were in the thymus, the higher the number of regulatory cells generated. That direct correlation raises interesting possibilities. One possibility is using BAFF, a nontoxic substance, to ramp up the B cell count of patients before transplant procedures. It will be very interesting to test whether or not that would prevent rejection.”