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mIgM-mediated splenic marginal zone B cells targeting of folic acid for immunological evasion. | LitMetric

mIgM-mediated splenic marginal zone B cells targeting of folic acid for immunological evasion.

Acta Pharm Sin B

Department of Pharmacology, School of Basic Medical Sciences & Department of Pharmacy, Shanghai Pudong Hospital, Fudan University, Shanghai 200032, China.

Published: February 2024

AI Article Synopsis

Article Abstract

Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital disabilities. Here we revealed the immunosuppressive effect of folic acid by targeting splenic marginal zone B (MZB) cells. Folic acid demonstrates avid binding with the Fc domain of immunoglobulin M (IgM), targeting IgM positive MZB cells to destabilize IgM-B cell receptor (BCR) complex and block immune responses. The induced anergy of MZB cells by folic acid provides an immunological escaping window for antigens. Covalent conjugation of folic acid with therapeutic proteins and antibodies induces immunological evasion to mitigate the production of anti-drug antibodies, which is a major obstacle to the long-term treatment of biologics by reducing curative effects and/or causing adverse reactions. Folic acid acts as a safe and effective immunosuppressant IgM-mediated MZB cells targeting to boost the clinical outcomes of biologics by inhibiting the production of anti-drug antibodies, and also holds the potential to treat other indications that adverse immune responses need to be transiently shut off.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10840397PMC
http://dx.doi.org/10.1016/j.apsb.2023.09.011DOI Listing

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