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LRBA regulates actin cytoskeleton dynamics through NMIIA during B cell immune responses
Elena Sindram1,2,3, Juan Eduardo Montero-Hernández4, Quentin Frenger5,6
1Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. elena.sindram@uniklinik-freiburg.de.
EMBO Reports
|June 12, 2026
Summary
Lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency impairs B cell function by disrupting actin cytoskeleton dynamics and immune synapse formation. This study identifies non-muscle myosin IIA (NMIIA) as a key LRBA interaction partner in B cells.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency causes severe B cell dysfunction, but mechanisms are unclear.
- B cell activation relies on cytoskeletal rearrangements and immune synapse formation.
Purpose of the Study:
- To investigate the role of LRBA in B cell activation and identify its interaction partners.
- To elucidate the mechanisms underlying B cell dysfunction in LRBA deficiency.
Main Methods:
- Co-immunoprecipitation to identify LRBA interaction partners.
- Analysis of B cell migration, F-actin polymerization, and B cell receptor (BCR) signaling.
- Assessment of immune synapse formation, including SMAC formation, MTOC translocation, and protein polarization.
- Evaluation of BCR-antigen complex internalization and non-muscle myosin IIA (NMIIA) activation.
Main Results:
- Non-muscle myosin IIA (NMIIA) identified as an LRBA interaction partner in B cells.
- LRBA deficiency leads to impaired B cell migration, F-actin polymerization, BCR signaling, and immune synapse formation.
- Reduced NMIIA activation (MLC phosphorylation) and disrupted co-localization of LRBA with active NMIIA observed in LRBA-deficient B cells.
- Impaired BCR-antigen complex internalization in LRBA-deficient B cells.
Conclusions:
- LRBA regulates actin cytoskeleton dynamics and immune synapse formation during B cell activation.
- LRBA interacts with NMIIA to modulate B cell function.
- Dysregulation of LRBA-NMIIA interaction contributes to defective humoral immunity in LRBA deficiency.
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