Autoreactive IgG and IgA B Cells Evolve through Distinct Subclass Switch Pathways in the Autoimmune Disease Pemphigus Vulgaris
| Autor: | Qi Zheng, Eun Jung Choi, Shantan Reddy, Xuming Mao, Christoph T. Ellebrecht, Eric M. Mukherjee, Aimee S. Payne |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Biology medicine.disease_cause General Biochemistry Genetics and Molecular Biology Epitope Subclass Autoimmunity 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine medicine Humans education B cell Autoimmune disease education.field_of_study B-Lymphocytes Pemphigus vulgaris Autoantibody medicine.disease Immunoglobulin A 030104 developmental biology medicine.anatomical_structure Immunoglobulin G Desmoglein 3 Immunology Pemphigus |
| Zdroj: | Cell reports. 24(9) |
| ISSN: | 2211-1247 |
| Popis: | Lineage analysis of autoreactive B cells can reveal the origins of autoimmunity. In the autoimmune disease pemphigus vulgaris (PV), desmoglein 3 (DSG3) and DSG1 autoantibodies are predominantly of the IgG4 subclass and less frequently of IgG1 and IgA subclasses, prompting us to investigate whether anti-DSG IgG4 B cells share lineages with IgG1, IgA1, and IgA2. Combining subclass-specific B cell deep sequencing with high-throughput antibody screening, we identified 80 DSG-reactive lineages from 4 PV patients. Most anti-DSG IgG4 B cells lacked clonal relationships to other subclasses and preferentially targeted DSG adhesion domains, whereas anti-DSG IgA frequently evolved from or to other subclasses and recognized a broader range of epitopes. Our findings suggest that anti-DSG IgG4 B cells predominantly evolve independently or diverge early from other subclasses and that IgA is most often not the origin of IgG autoreactivity in PV. These data provide insight into how autoreactivity diversifies across B cell subclasses. |
| Databáze: | OpenAIRE |
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