LRBA regulates actin cytoskeleton dynamics through NMIIA during B cell immune responses

Abstract

Patients with lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency typically suffer from severe B cell dysfunction. However, the underlying mechanisms remain incompletely understood. In this study, we identify non-muscle myosin IIA (NMIIA) as an interaction partner of LRBA in B cells, and uncover a role for LRBA in regulating actin cytoskeleton dynamics during B cell activation. LRBA-deficient B cells exhibit abnormal migration, impaired F-actin polymerization, and reduced B cell receptor signalling and polarization upon activation. In addition, LRBA deficiency severely disrupts immune synapse formation as evidenced by diminished central SMAC formation, reduced microtubule organizing center translocation and disrupted BCR and lysosome polarization. Consistent with these defects, internalization of the BCR-antigen complex is also impaired. Mechanistically, NMIIA activation, assessed by myosin light chain (MLC) phosphorylation, is reduced in LRBA-deficient cells. In addition, LRBA co-localizes with active NMIIA during both migration and immune synapse formation. Collectively, our findings establish LRBA as an important regulator of cytoskeleton dynamics during B cell activation, which may contribute to the defective humoral immunity observed in LRBA-deficient patients.

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BibTeX RIS

BibTeX

@article{sindram2026lrba,
  title = {{LRBA regulates actin cytoskeleton dynamics through NMIIA during B cell immune responses}},
  author = {Elena Sindram and Juan Eduardo Montero-Hernández and Quentin Frenger and Hannah van Dijk and Anna Lang and Vanessa Zeidler and Rebecca Marsiske and Manuel Rhiel and Kerstin Geiger and Tatjana Cornu and Emily Mace and Volker Spindler and Joern Dengjel and Frédéric Gros and Bodo Grimbacher and Fernando Sepulveda and Yolanda Carrasco and Virginia Andreani and Laura Gámez-Díaz},
  journal = {EMBO Reports},
  year = {2026},
  month = jun,
  doi = {10.1038/s44319-026-00831-3},
  url = {https://hal.science/hal-05823601v1},
  note = {CC BY},
}

RIS

TY  - JOUR
TI  - LRBA regulates actin cytoskeleton dynamics through NMIIA during B cell immune responses
AU  - Elena Sindram
AU  - Juan Eduardo Montero-Hernández
AU  - Quentin Frenger
AU  - Hannah van Dijk
AU  - Anna Lang
AU  - Vanessa Zeidler
AU  - Rebecca Marsiske
AU  - Manuel Rhiel
AU  - Kerstin Geiger
AU  - Tatjana Cornu
AU  - Emily Mace
AU  - Volker Spindler
AU  - Joern Dengjel
AU  - Frédéric Gros
AU  - Bodo Grimbacher
AU  - Fernando Sepulveda
AU  - Yolanda Carrasco
AU  - Virginia Andreani
AU  - Laura Gámez-Díaz
PY  - 2026
DA  - 2026/06/12
JO  - EMBO Reports
DO  - 10.1038/s44319-026-00831-3
UR  - https://hal.science/hal-05823601v1
AB  - Patients with lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency typically suffer from severe B cell dysfunction. However, the underlying mechanisms remain incompletely understood. In this study, we identify non-muscle myosin IIA (NMIIA) as an interaction partner of LRBA in B cells, and uncover a role for LRBA in regulating actin cytoskeleton dynamics during B cell activation. LRBA-deficient B cells exhibit abnormal migration, impaired F-actin polymerization, and reduced B cell receptor signalling and polarization upon activation. In addition, LRBA deficiency severely disrupts immune synapse formation as evidenced by diminished central SMAC formation, reduced microtubule organizing center translocation and disrupted BCR and lysosome polarization. Consistent with these defects, internalization of the BCR-antigen complex is also impaired. Mechanistically, NMIIA activation, assessed by myosin light chain (MLC) phosphorylation, is reduced in LRBA-deficient cells. In addition, LRBA co-localizes with active NMIIA during both migration and immune synapse formation. Collectively, our findings establish LRBA as an important regulator of cytoskeleton dynamics during B cell activation, which may contribute to the defective humoral immunity observed in LRBA-deficient patients.
SN  - 1469-221X
SN  - 1469-3178
ER  -

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