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Generation of T follicular helper cells in vitro : requirement for B ‐cell receptor cross‐linking and cognate B‐ and T‐cell interaction
Author(s) -
Kolenbrander Anne,
Grewe Bastian,
Nemazee David,
Überla Klaus,
Temchura Vladimir
Publication year - 2018
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12834
Subject(s) - biology , microbiology and biotechnology , b cell , b cell receptor , naive b cell , t cell , epitope , antigen presenting cell , cytotoxic t cell , in vitro , antibody , immunology , immune system , genetics
Summary The minimum requirements for in vitro modelling of natural CD 4 + T‐cell differentiation into T follicular helper ( Tfh ) cells are still under investigation. We co‐cultured wild‐type and T‐cell receptor ( TCR ) transgenic CD 4 + T cells from naive mice with dendritic cells and B‐cell receptor ( BCR ) transgenic B cells in the presence of HIV ‐derived virus‐like particles containing matched B‐cell and T‐cell epitopes. This co‐culturing induced co‐expression of Tfh ‐master regulator transcription factor BCL ‐6 and CXCR 5 in up to 10% of the wild‐type and up to 40% of the TCR ‐transgenic CD 4 + T cells. Phenotypic markers, production of interleukin‐21 and isotype switching of the B cells to IgG1 further indicated a helper function of the induced Tfh cells in vitro . Dendritic cells supported the generation of functional Tfh cells, but were unable to induce them without cognate B cells. Hence, our study presents a robust experimental system for efficient generation of functionally active Tfh cells in vitro and confirms the importance of cognate B‐ and T‐cell cross‐talk for the Tfh differentiation process.