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. 2025 Dec 20;10(1):407.
doi: 10.1038/s41392-025-02510-6.

Anti-BCMA CAR-T cells attenuate microglial activation in progressive multiple sclerosis: indicating a plasma cell-microglia crosstalk

Fatme S Ismail  1 , Hans-Peter Hartung #  2   3   4 , Nico Melzer #  2
Affiliations

Anti-BCMA CAR-T cells attenuate microglial activation in progressive multiple sclerosis: indicating a plasma cell-microglia crosstalk

Fatme S Ismail et al. Signal Transduct Target Ther. .
No abstract available

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Conflict of interest statement

Competing interests: FS.I. reports no conflicts of interest. HP.H. has received honoraria from Boehringer Ingelheim, Merck Darmstadt KgA and Novartis for serving on data monitoring committees, for work not related to the present manuscript. N.M. reported receiving grants from the German Federal Ministry of Education and Research, for work not related to the present manuscript.

Figures

Fig. 1
Fig. 1
During B cell differentiation, B-cell maturation antigen (BCMA) is expressed on late-stage B cells (after differentiation to immunoglobulin-secreting cells), short-lived plasmablasts and long-lived plasma cells, as recently shown with a BCMA reporter mouse model. However, differences in BCMA expression between mouse and human immune cells have been found and should be considered. BCMA is necessary for the survival of long-lived plasma cells, production of antibodies, class switch of immunoglobulins. A proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF) are physiological ligands for BCMA. CD19 and BCMA are the most frequently used B-cell target antigens in CAR constructs for autoimmune diseases. Anti-BCMA CAR-T cell treatment in progressive Multiple sclerosis led to deep depletion of BCMA-expressing B cells/plasma cells in compartments of the central nervous system and attenuated microglial activation, resulting in significant functional improvement during a 9-month follow-up. The intriguing effect of anti-BCMA CAR-T cells on microglia might indicate a plasma cell-microglia crosstalk. CAR chimeric antigenreceptor, CD19 cluster of differentiation 19, GC B germinal center B cells. Figure created in BioRender. Ismail, F. (2025) https://BioRender.com/z2pozz2
See this image and copyright information in PMC

References

    1. Qin, C. et al. Anti-BCMA CAR-T therapy in patients with progressive multiple sclerosis. Cell10.1016/J.CELL.2025.09.020 (2025). - PubMed
    1. Fischbach, F. et al. CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis. Medicine5, 550–558.e2 (2024). - DOI - PubMed
    1. Kumar, G. et al. CNS autoimmune responses in BCMA-deficient mice provide insight for the failure of atacicept in MS. Neurol. Neuroimmunol. Neuroinflammation8, e973 (2021). - DOI - PMC - PubMed
    1. Van Oekelen, O. et al. Neurocognitive and hypokinetic movement disorder with features of Parkinsonism following BCMA-targeting CAR-T cell therapy. Nat. Med.27, 2099 (2021). - DOI - PMC - PubMed
    1. Geraghty, A. C. et al. Immunotherapy-related cognitive impairment after CAR T cell therapy in mice. Cell188, 3238–3258.e25 (2025). - DOI - PMC - PubMed

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