EFB Dengue Literature Review

FCRL5

2 min read

FCRL5

Overview

FCRL5 (Fc Receptor-Like 5; also FcRH5) is a member of the Fc receptor-like family. Unlike FcRH4 (FCRL4), which mediates hypo-responsiveness in HIV exhausted memory cells, FCRL5 is induced by BCR signalling and can drive naive B cell proliferation. FCRL5 is expressed on DN2 and aNAV B cells in SLE and on CD21⁻ atypical memory cells in malaria, making it a cross-disease marker of extrafollicular/atypical B cell identity.

Key Points from Literature

  • Expressed on DN2 and aNAV: FCRL5 surface expression (MFI) is elevated on DN2 and aNAV cells relative to SWM, rNAV, and DN1 in both SLE and HCD. Validated at both RNA and protein level (see Jenks2018 - DN2 B Cells and EF Pathway in SLE).

  • FCRL4⁻/FCRL5⁺ pattern distinguishes SLE DN2 from HIV exhausted memory: SLE DN2 cells are FCRL4⁻ FCRL5⁺; HIV CD21⁻ DN cells are FCRL4⁺. A similar FCRL4⁻/FCRL5⁺ pattern has been reported in malaria atypical memory cells (citing Portugal et al. 2015). Despite FCRL5 expression, SLE DN2 cells retain intact proximal BCR signalling (BLNK phosphorylation after anti-IgG stimulation) — functionally distinct from HIV exhausted cells (see Jenks2018 - DN2 B Cells and EF Pathway in SLE).

  • In vitro upregulation: FCRL5 is upregulated on in vitro-generated DN2 cells (from rNAV + TLR7/IFN-γ/IL-21 cultures), confirming it is acquired during EF differentiation (see Jenks2018 - DN2 B Cells and EF Pathway in SLE).

  • FcRL5 as therapeutic target: FCRL5 is one of two preferred surface targets (alongside SLAMF7) for selective ABC/DN2 depletion within the B cell compartment — sparing resting naive and conventional memory cells (see Sanz2025 - Human Atypical B Cells Overview, review).

  • T-bet⁺/FcRL5⁺ defines memory ABC within CD27⁺ compartment: In influenza vaccination responses, T-bet⁺/FcRL5⁺ CD27⁺ memory ABC cells are poised for ASC differentiation and correlate with long-lived antibody responses, while T-bet⁻/FcRL5⁻ canonical memory cells have stem-like central memory properties (see Sanz2025 - Human Atypical B Cells Overview, review citing Nellore et al. 2023).

  • T-bet or FcRL5 can substitute for CD11c in gating: These markers identify similar populations when used vs. CXCR5 in the DN gate, providing flexibility for panel design (see Sanz2025 - Human Atypical B Cells Overview, review, Figure 2).

Contradictions & Debates

None documented in current wiki sources.

DN2 B Cell, FcRH4, Activated Naive B Cell, Double-Negative B Cell, SLAMF7, T-bet, Extrafollicular Response

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