CD4 T Cells That Promote Extrafollicular B Cell Responses

Abstract

The role of follicular helper T cells (TFH) in development and maintenance of the germinal center is well known; however the role of T cells in the extrafollicular B cell response is less understood. We have described a novel subset of activated IL‐21 producing CD4 T cells that are located at extrafollicular sites in murine lupus. These cells are CXCR5lo and are marked by downregulation of P selectin glycoprotein ligand 1 (PSGL1). To determine if the IL‐21+ CXCR5lo PSGL1lo population exists in a normal immune response, we used adoptive transfer of ovalbumin (ova) specific TCR transgenic CD4 T cells to track their development following ova immunization. We find that PSGL1lo cells arise following ova immunization, with significant expansion when the antigen is administered chronically. Like TFH cells, this population requires ICOS for its development; however, unlike the former, B cells do not appear to be required. In the absence of the PSGL1lo population, isotype switched antibody production to ova is lost. These cells make IL‐21; however, only a subset makes IL‐4 and is CXCR5hi. By microscopy, PSGL1lo cells are found in the B cell follicle and at extrafollicular sites. Based on this data, we hypothesize that IL‐21+ CXCR5lo PSGL1lo cells are important for extrafollicular responses. We have termed this novel population T helper extrafollicular cells or THEF cells.