B cell activation required for antibody production and the establishment of immunological memory is initiated by antigen recognition through the B cell receptor (BCR) and subsequent internalization of antigen for presentation to T cells. After activation, B cells proliferate and differentiate into plasma cells or memory B cells. The mechanism involved in this B cell fate decision has been recently explored and a new theory has been proposed based on the existence of an asymmetrical B cell division (1). This theory assumes the unequal inheritance of antigen between daughter cells due to antigen being rapidly polarized in a unique compartment that is maintained along B cell division. This polarity abolishes the uniform distribution of antigen vesicles between daughter cells, generating two functionally different B cells.
This proposal is focused on understanding how this initial antigen polarity is established and maintained and what is its role in B cell activation. Furthermore, the functional significance of the asymmetrical B cell decision will be analyzed in vitro and in vivo. In addition, possible new parameters asymmetrically distributed that could also determine B cell fate decisions will be evaluated.
During this project, a huge range of techniques including state-of-the-art microscopy (in vitro and in vivo methodologies), flow cytometry systems (multiparametric analysis and ImageStream) will be used and advance mathematical analysis approaches will be developed.
Results from this proposal will contribute to the general knowledge of immunological responses, but more precisely will explain how different B cell populations are originated after B cell activation, a key step that is deregulated in some diseases such as cancer.
1. O. Thaunat et al., Science 335, 475 (Feb 26, 2012).
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