Follicular helper T cells (TFH) are essential for the formation of germinal centers (GC) during a T-dependent immune response, providing critical factors that promote memory B cell and plasma cell development. Differentiation and function of TFH cells are dependent upon their movement out of the T cell zone and into the B cell follicle, a process regulated by modulation of chemokine receptor expression. Here we explore the role of the secondary lymphoid organ homing molecule, PSGL1, as a T zone retention signal, demonstrating that its downregulation on TFH cells is necessary for their migration out of the T cell zone and into the follicle. Upon immunization of PSGL1-intact and -deficient mice, we found that the latter had an increase in TFH cells and GC B cells in lymph nodes and spleen, and enlarged GCs with enhanced numbers of T cell infiltrates, compared to wild type controls. Following adoptive transfer, a higher frequency of PSGL1-deficient T cells localized to B cell follicles and GCs compared to controls, whereas retroviral over-expression of PSGL1, preventing its downregulation, led to exclusion of T cells from follicles and GCs. Consistent with these observations was the finding in chromatin immunoprecipitation assays that Bcl6, the lineage-specific transcription factor of TFH cells, bound the psgl1 gene. These data reveal that PSGL1 downregulation on TFH cells is required for their migration within lymphoid organs and function during a TD immune response.
- Copyright © 2011 by The American Association of Immunologists, Inc.