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. 2022 Sep;74(9):1556-1568.
doi: 10.1002/art.42157. Epub 2022 Aug 2.

Plasmablast-like Phenotype Among Antigen-Experienced CXCR5-CD19low B Cells in Systemic Lupus Erythematosus

Franziska Szelinski  1 , Ana Luisa Stefanski  2 , Eva Schrezenmeier  1 , Hector Rincon-Arevalo  3 , Annika Wiedemann  2 , Karin Reiter  1 , Jacob Ritter  1 , Marie Lettau  1 , Van Duc Dang  1 , Sebastian Fuchs  4 , Andreas P Frei  4 , Tobias Alexander  1 , Andreia C Lino  1 , Thomas Dörner  1
Affiliations

Plasmablast-like Phenotype Among Antigen-Experienced CXCR5-CD19low B Cells in Systemic Lupus Erythematosus

Franziska Szelinski et al. Arthritis Rheumatol. 2022 Sep.

Abstract

Objective: Altered composition of the B cell compartment in the pathogenesis of systemic lupus erythematosus (SLE) is characterized by expanded plasmablast and IgD-CD27- double-negative B cell populations. Previous studies showed that double-negative B cells represent a heterogeneous subset, and further characterization is needed.

Methods: We analyzed 2 independent cohorts of healthy donors and SLE patients, using a combined approach of flow cytometry (for 16 healthy donors and 28 SLE patients) and mass cytometry (for 18 healthy donors and 24 SLE patients) and targeted RNA-Seq analysis. To compare B cell subset formation during the acute immune response versus that during autoimmune disease, we investigated healthy donors at various time points after receipt of the BNT162b2 messenger RNA COVID-19 vaccine and patients with acute SARS-CoV-2 infection, using flow cytometry.

Results: We found that IgD-CD27+ switched and atypical IgD-CD27- memory B cells, the levels of which were increased in SLE patients, represented heterogeneous populations composed of 3 different subsets each. CXCR5+CD19intermediate , CXCR5-CD19high , and CXCR5-CD19low populations were found in the switched memory and double-negative compartments, suggesting the relatedness of IgD-CD27+ and IgD-CD27- B cells. We characterized a hitherto unknown and antigen-experienced CXCR5-CD19low subset that was enhanced in SLE patients, had a plasmablast phenotype with diminished B cell receptor responsiveness, and expressed CD38, CD95, CD71, PRDM1, XBP1, and IRF4. Levels of CXCR5-CD19low subsets were increased and correlated with plasmablast frequencies in SLE patients and in healthy donors who received BNT162b2, suggesting their interrelationship and contribution to plasmacytosis. The detection of CXCR5-CD19low B cells among both CD27+ and CD27- populations calls into question the role of CD27 as a reliable marker of B cell differentiation.

Conclusion: Our data suggest that CXCR5-CD19low B cells are precursors of plasmablasts. Thus, cotargeting this subset may have therapeutic value in SLE.

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References

REFERENCES

    1. Odendahl M, Jacobi A, Hansen A, Feist E, Hiepe F, Burmester GR, et al. Disturbed peripheral B lymphocyte homeostasis in systemic lupus erythematosus. J Immunol 2000;165:5970-9.
    1. Mei HE, Hahne S, Redlin A, Hoyer BF, Wu K, Baganz L, et al. Plasmablasts with a mucosal phenotype contribute to plasmacytosis in systemic lupus erythematosus. Arthritis Rheumatol 2017;69:2018-28.
    1. Wei C, Anolik J, Cappione A, Zheng B, Pugh-Bernard A, Brooks J, et al. A new population of cells lacking expression of CD27 represents a notable component of the B cell memory compartment in systemic lupus erythematosus. J Immunol 2007;178:6624-33.
    1. Souto-Carneiro MM, Mahadevan V, Takada K, Fritsch-Stork R, Nanki T, Brown M, et al. Alterations in peripheral blood memory B cells in patients with active rheumatoid arthritis are dependent on the action of tumour necrosis factor. Arthritis Res Ther 2009;11:R84.
    1. Pararasa C, Zhang N, Tull TJ, Chong MH, Siu JH, Guesdon W, et al. Reduced CD27(-)IgD(-) B cells in blood and raised CD27(-)IgD(-) B cells in gut-associated lymphoid tissue in inflammatory bowel disease. Front Immunol 2019;10:361.

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