AUTHOR=Mamidi Murali K. , Huang Jifeng , Honjo Kazuhito , Li Ran , Tabengwa Edlue M. , Neeli Indira , Randall Nar’asha L. , Ponnuchetty Manasa V. , Radic Marko , Leu Chuen-Miin , Davis Randall S. 

TITLE=FCRL1 immunoregulation in B cell development and malignancy

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1251127

DOI=10.3389/fimmu.2023.1251127

ISSN=1664-3224

ABSTRACT=<p>Immunotherapeutic targeting of surface regulatory proteins and pharmacologic inhibition of critical signaling pathways has dramatically shifted our approach to the care of individuals with B cell malignancies. This evolution in therapy reflects the central role of the B cell receptor (BCR) signaling complex and its co-receptors in the pathogenesis of B lineage leukemias and lymphomas. Members of the Fc receptor-like gene family (<italic>FCRL1-6</italic>) encode cell surface receptors with complex tyrosine-based regulation that are preferentially expressed by B cells. Among them, FCRL1 expression peaks on naïve and memory B cells and is unique in terms of its intracellular co-activation potential. Recent studies in human and mouse models indicate that FCRL1 contributes to the formation of the BCR signalosome, modulates B cell signaling, and promotes humoral responses. Progress in understanding its regulatory properties, along with evidence for its over-expression by mature B cell leukemias and lymphomas, collectively imply important yet unmet opportunities for FCRL1 in B cell development and transformation. Here we review recent advances in FCRL1 biology and highlight its emerging significance as a promising biomarker and therapeutic target in B cell lymphoproliferative disorders.</p>