CD52 is elevated on B cells of SLE patients and regulates B cell function

• Verfasst von: Bhamidipati, Kartik [VerfasserIn]
• Verfasst von: Silberstein, John L. [VerfasserIn]
• Verfasst von: Chaichian, Yashaar [VerfasserIn]
• Verfasst von: Baker, Matthew C. [VerfasserIn]
• Verfasst von: Lanz, Tobias [VerfasserIn]
• Verfasst von: Zia, Amin [VerfasserIn]
• Verfasst von: Rasheed, Yusuf S. [VerfasserIn]
• Verfasst von: Cochran, Jennifer R. [VerfasserIn]
• Verfasst von: Robinson, William H. [VerfasserIn]
• Titel: CD52 is elevated on B cells of SLE patients and regulates B cell function
• Verf.angabe: Kartik Bhamidipati, John L. Silberstein, Yashaar Chaichian, Matthew C. Baker, Tobias V. Lanz, Amin Zia, Yusuf S. Rasheed, Jennifer R. Cochran and William H. Robinson
• E-Jahr: 2021
• Jahr: 04 February 2021
• Umfang: 17 S.
• Fussnoten: Gesehen am 15.04.2021
• Titel Quelle: Enthalten in: Frontiers in immunology
• Ort Quelle: Lausanne : Frontiers Media, 2010
• Jahr Quelle: 2021
• Band/Heft Quelle: 11(2021), Artikel-ID 626820, Seite 1-17
• ISSN Quelle: 1664-3224
• DOI: doi:10.3389/fimmu.2020.626820
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Autoimmunity
• Sach-SW: B cell receptor signaling
• Sach-SW: B cells
• Sach-SW: glycoprotein
• Sach-SW: systemic lupus erythematosus
• K10plus-PPN: 1755011040

Abstract

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by B cell dysregulation and breaks in tolerance that lead to the production of pathogenic autoantibodies. We performed single-cell RNA sequencing of B cells from healthy and SLE individuals which revealed upregulated CD52 expression in SLE patients. We further demonstrate that SLE patients exhibit significantly increased levels of B cell surface CD52 expression and plasma soluble CD52, and levels of soluble CD52 positively correlate with measures of lupus disease activity. Using CD52-deficient JeKo-1 cells, we show that cells lacking surface CD52 expression are hyperresponsive to B cell receptor (BCR) signaling, suggesting an inhibitory role for the surface-bound protein. In donor B cells, antigen-specific BCR-activation initiated CD52 cleavage in a phospholipase C dependent manner, significantly reducing cell surface levels. Experiments with recombinant CD52-Fc showed that soluble CD52 inhibits BCR signaling in a manner partially-dependent on Siglec-10. Moreover, incubation of unstimulated B cells with CD52-Fc resulted in the reduction of surface immunoglobulin and CXCR5. Prolonged incubation of B cells with CD52 resulted in the expansion of IgD+IgMlo anergic B cells. In summary, our findings suggest that CD52 functions as a homeostatic protein on B cells, by inhibiting responses to BCR signaling. Further, our data demonstrate that CD52 is cleaved from the B cell surface upon antigen engagement, and can suppress B cell function in an autocrine and paracrine manner. We propose that increased expression of CD52 by B cells in SLE represents a homeostatic mechanism to suppress B cell hyperactivity.