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Plasmablast-like Phenotype Among Antigen-Experienced CXCR5-CD19 low B Cells in Systemic Lupus Erythematosus.
- Source :
-
Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2022 Sep; Vol. 74 (9), pp. 1556-1568. Date of Electronic Publication: 2022 Aug 02. - Publication Year :
- 2022
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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.<br />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.<br />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+CD19 <superscript>intermediate</superscript> , CXCR5-CD19 <superscript>high</superscript> , and CXCR5-CD19 <superscript>low</superscript> 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-CD19 <superscript>low</superscript> 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-CD19 <superscript>low</superscript> 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-CD19 <superscript>low</superscript> B cells among both CD27+ and CD27- populations calls into question the role of CD27 as a reliable marker of B cell differentiation.<br />Conclusion: Our data suggest that CXCR5-CD19 <superscript>low</superscript> B cells are precursors of plasmablasts. Thus, cotargeting this subset may have therapeutic value in SLE.<br /> (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
- Subjects :
- Antigens, CD19 genetics
Antigens, CD19 metabolism
BNT162 Vaccine
COVID-19 Vaccines
Humans
Immunoglobulin D
Phenotype
Receptors, CXCR5 genetics
Receptors, CXCR5 metabolism
SARS-CoV-2
B-Lymphocyte Subsets metabolism
COVID-19
Lupus Erythematosus, Systemic genetics
Lupus Erythematosus, Systemic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2326-5205
- Volume :
- 74
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Arthritis & rheumatology (Hoboken, N.J.)
- Publication Type :
- Academic Journal
- Accession number :
- 35507291
- Full Text :
- https://doi.org/10.1002/art.42157