FCRL1 immunoregulation in B cell development and malignancy

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

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

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 (FCRL1-6) 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.

Original languageEnglish
Article number1251127
JournalFrontiers in Immunology
Volume14
DOIs
StatePublished - 2023

Keywords

  • B cell receptor
  • B cells
  • FCRL1
  • immunotherapy
  • lymphocyte development
  • malignancy
  • signaling

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