Novel pathways in T lymphocyte differentiation and function

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The ability to generate high-affinity antibodies to diverse infectious agents (i.e. humoral immunity) is a fundamental property of the vertebrate immune system and ensures host survival. The humoral immune response requires highly coordinated interactions between B lymphocytes (which possess antibody-producing potential) and “helper” T cells. These interactions are mediated by a subset of helper T cells termed T follicular helper (Tfh) cells that provide direct help to B cells through provision of membrane-bound co-stimulatory molecules and secretion of polarizing cytokines. We have previously shown that Tfh cells provide critical sources of interleukin (IL)-4 and IL-21 required for the generation of humoral immune responses in the context of immunization (King et al, Nature Immunology, 2012) and parasitic helminth infection (King and Mohrs, Journal of Experimental Medicine, 2009). This proposal builds on these findings to identify previously undescribed molecules and signaling pathways that specifically control T cell differentiation and function.