SHIP-1 is sufficient for the recruitment of FCRL1 to the BCR 2957

Abstract Description Fc receptor-like 1 (FCRL1) is a key cell surface receptor predominantly expressed on the surface of B cells where it plays a critical role in modulating B cell receptor (BCR) signalling. Understanding the role of FCRL1 in signal modulation can reveal how it influences the immune response and downstream signalling pathways. In this study, we investigated the interactions between FCRL1 and the BCR under different activation states using confocal microscopy. Mouse A20 B cells and primary murine B cells were exposed to conditions mimicking antigen stimulation by cross-linking BCRs to trigger clustering signalling cascades. Co-localization of FCRL1 with the BCR was then quantified and compared between activated and resting cells. Our results revealed that upon BCR stimulation, FCRL1 co-localizes with the BCR complex, suggesting its recruitment is linked to BCR activation. We examined cell lines with modifications to FCRL1 functional domains. We found that FCRL1 co-localizes with the BCR complex, involving the adaptor protein GRB2 and the Y281 residue of FCRL1. Additionally, we explored the involvement of SHIP-1, a regulatory phosphatase that binds FCRL1 in a phosphotyrosine and GRB2-dependent manner. A mutant of FCRL1, with its tyrosine residue ablated, retained the ability to co-localize if fused with the SH2 domain of SHIP-1 being sufficient for co-localization. Furthermore, our data show that through interactions with SHIP-1 and GRB2, FCRL1 modulates ERK activation. Funding Sources NIH 1R15AI174170-01 Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)