TY - JOUR TI - Tuning of in vivo cognate B-T cell interactions by Intersectin 2 is required for effective anti-viral B cell immunity AU - Burbage, Marianne AU - Gasparrini, Francesca AU - Aggarwal, Shweta AU - Gaya, Mauro AU - Arnold, Johan AU - Nair, Usha AU - Way, Michael AU - Bruckbauer, Andreas AU - Batista, Facundo D A2 - Dustin, Michael L A2 - Nussenzweig, Michel C VL - 7 PY - 2018 DA - 2018/01/16 SP - e26556 C1 - eLife 2018;7:e26556 DO - 10.7554/eLife.26556 UR - https://doi.org/10.7554/eLife.26556 AB - Wiskott-Aldrich syndrome (WAS) is an immune pathology associated with mutations in WAS protein (WASp) or in WASp interacting protein (WIP). Together with the small GTPase Cdc42 and other effectors, these proteins participate in the remodelling of the actin network downstream of BCR engagement. Here we show that mice lacking the adaptor protein ITSN2, a G-nucleotide exchange factor (GEF) for Cdc42 that also interacts with WASp and WIP, exhibited increased mortality during primary infection, incomplete protection after Flu vaccination, reduced germinal centre formation and impaired antibody responses to vaccination. These defects were found, at least in part, to be intrinsic to the B cell compartment. In vivo, ITSN2 deficient B cells show a reduction in the expression of SLAM, CD84 or ICOSL that correlates with a diminished ability to form long term conjugates with T cells, to proliferate in vivo, and to differentiate into germinal centre cells. In conclusion, our study not only revealed a key role for ITSN2 as an important regulator of adaptive immune-response during vaccination and viral infection but it is also likely to contribute to a better understanding of human immune pathologies. KW - B cells KW - antibody responses KW - B-T interactions KW - SLAM family receptors KW - Wiskott-Aldrich syndrome JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -