3-D study of immune cell interactions reveals details of an effective antibody response
The immune system is constantly manufacturing new immune cells to protect the body from invasion by microbial pathogens; cells of the adaptive immune response (T cells and B cells) are central to the immune system's capacity to fight off disease. B cells and helper T cells must interact to organize an effective B-cell antibody response, but until recently there has been no way to observe the directed migration processes that guide the lymphocytes to the zone where they can interact. In a new study published in the open-access journal PLoS Biology, researchers at the University of California at San Francisco and the University of California at Irvine used a groundbreaking technology called two-photon microscopy to visually inspect intact lymph nodes extracted from mice to investigate this lymphocyte rendezvous.
After maturing in different organs of the body, T and B cells travel to distinct regions in the spleen and lymph nodes - B cells amassing in follicles and T cells in T zones - in search of alien antigens. Upon encountering antigens, B and T lymphocytes migrate to the edges of their respective zones and compare notes. In the study led by Takaharu Okada and Jason Cyster and Mark Miller and Mike Cahalan, the authors used two-photon microscopy to directly observe the migration processes that guide the lymphocytes to the zone where they can interact.
This interaction, the authors discovered, involves a combination of random and directed behaviors: B cells that have encountered antigen first move randomly along the follicle outskirts. Then they undergo directed migration near the follicle/T-zone border as they home in on their helper T counterparts, moving more or less along a straight line. The B cells require the chemokine receptor CCR7 to follow directions to the T zone - which contains an abundant supply of CCR7's stimulating protein, CCL21. Finally, the authors observed that once in the T zone, B cells form stable interactions only with activated helper T cells that share a cognate antigen.
Thanks to the T lymphocyte–B lymphocyte dynamics outlined here, immunologists have new avenues for exploring these questions to further elucidate the complex interactions underlying an effective antibody attack.
Source: Eurekalert & others
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