Mentor: Timothy Wilson, Ph.D.

B Cells are a type of lymphocyte whose primary purpose is to generate highly specific antibodies in response to a foreign antigen. The B cell receptor (BCR) signaling pathway regulates B cell activation, and Fc receptor-like proteins may contribute to this pathway’s activation or inhibition. Previous studies have demonstrated that Fc receptor-like protein 1 (FCRL1) is found on B cell plasma membranes, associating with the BCR and enhancing the activation of the B cell. Also, growth factor receptor-bound 2 (Grb2) and Grb2-related adaptor protein (GRAP) are required to activate the extracellular signal regulated kinase pathway (ERK), which is necessary for proper B cell development in hematopoietic cells and for the formation of memory B cells. GRAP may function to recruit FCRL1 to the BCR, and therefore, determination of FCRL1 localization and function of GRAP within the localization cascade is a relevant and important field to further our understanding of B cell activation.

In all B cells, one of the main activating pathways of the BCR is the immunoreceptor tyrosine-based activation motif (ITAM), which leads to the cleavage of PIP2, resulting in a DAG/IP3 pathway that opens a ligand gated Ca2+ channel and culminates in an increase of intracellular Ca2+ concentrations. This concludes with B cell activation and transcriptional changes. However, in B cells with membrane bound IgE and IgG molecules, the immunoglobulin tail tyrosine (ITT) motif recruits growth factor receptor-bound 2 (Grb2), drastically amplifying second messenger production and skipping many of the earlier steps in the ITAM, leading directly to the DAG/IP3 pathway. GRAP and Grb2 are also required to activate the extracellular signal regulated kinase (ERK) pathway through the ITAM in hematopoietic cells.

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