Multifaceted B cell Activation by Retroviruses

Purpose and goal

The project aimed to investigate the cellular process of B cell activation, plasma cell differentiation and antibody response upon exposure to T-independent (TI) antigens. It therefore offers the possibility to gain new insights into B cell biology that can be applied for new vaccine approaches. The project used unique mouse models carrying random genetic mutations and displaying defect responses to TI immunization. Mutations in two completely non-related genes were shown to be important during this process; Nfkbid and Flcn, encoding IkBNS and Folliculin, respectively.

Expected results and effects

The VINNMER-Marie Curie fellowship gave me the opportunity to continue my scientific career in an international environment and made me develop into an independent researcher, both through the scientific work with visits to the collaboration laboratory in Dallas and through supervision of students and meetings with my mentors. In terms of data obtained, the project identified two proteins important for plasma cell differentiation and the outcome could generate knowledge that can be applied to develop new vaccine approaches.

Planned approach and implementation

The project used in vitro and in vivo methods and employed techniques of molecular biology as well as of cellular immunology. Based on the screen for ENU-mutagenized mice that show altered responses to immunization, unique mouse models were identified by the laboratories of Gunilla Karlsson Hedestam at Karolinska Institutet, and Bruce Beutler at the University of Texas, Southwestern. The identified models were used in the current project to further investigate the implications that these point mutations might have for B cell function and for humoral immune responses.