B cells in T follicular helper cell development and function: separable roles in delivery of ICOS ligand and antigen

• Published in: The Journal of immunology (1950) 2014-04, Vol.192 (7), p.3166-3179
• Main Authors: Weinstein, Jason S, Bertino, Sarah A, Hernandez, Sairy G, Poholek, Amanda C, Teplitzky, Taylor B, Nowyhed, Heba N, Craft, Joe
• Format: Article
• Language: English
• Subjects: Animals; Antigens - immunology; Antigens, CD19 - genetics; Antigens, CD19 - immunology; Antigens, CD19 - metabolism; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Cell Proliferation; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Flow Cytometry; Inducible T-Cell Co-Stimulator Ligand - genetics; Inducible T-Cell Co-Stimulator Ligand - immunology; Inducible T-Cell Co-Stimulator Ligand - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Microscopy, Confocal; Nitrophenols - immunology; Ovalbumin - immunology; Phenylacetates - immunology; Proto-Oncogene Proteins c-bcl-6; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1302617

B cells are required for follicular Th (Tfh) cell development, as is the ICOS ligand (ICOS-L); however, the separable contributions of Ag and ICOS-L delivery by cognate B cells to Tfh cell development and function are unknown. We find that Tfh cell and germinal center differentiation are dependent on cognate B cell display of ICOS-L, but only when Ag presentation by the latter is limiting, with the requirement for B cell expression of ICOS-L overcome by robust Ag delivery. These findings demonstrate that Ag-specific B cells provide different, yet compensatory, signals for Tfh cell differentiation, while reconciling conflicting data indicating a requirement for ICOS-L expression on cognate B cells for Tfh cell development with those demonstrating that the latter requirement could be bypassed in lieu of that tendered by noncognate B cells. Our findings clarify the separable roles of delivery of Ag and ICOS-L by cognate B cells for Tfh cell maturation and function, and have implications for using therapeutic ICOS blockade in settings of abundantly available Ag, such as in systemic autoimmunity.