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| Status |
Public on Jun 22, 2023 |
| Title |
Transcriptomic diversity and overlapping clonality across subsets of antibody-secreting and memory B cells from spontaneous germinal centers |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Affinity matured self-reactive antibodies are found in autoimmune diseases like systemic lupus erythematous. Here we used fate-mapping reporter mice and single cell transcriptomics coupled to antibody repertoire analysis to characterize the post-germinal center (GC) B cell compartment in a new mouse model of autoimmunity. Antibody secreting cells (ASCs) and memory B cells (MemBs) from spontaneous GCs grouped into multiple subclusters. ASCs matured into two terminal clusters, with distinct secretion, antibody repertoire and metabolic profiles. MemBs contained FCRL5+ and CD23+ subsets, with different in vivo localization in the spleen. GC-derived FCRL5+ MemBs share transcriptomic and repertoire properties with atypical B cells found in aging and infection and localize to the marginal zone, suggesting a similar contribution to rapid recall responses. While transcriptomically diverse, ASC and MemB subsets maintained an underlying clonal redundancy. Therefore, self-reactive clones could escape subset-targeting therapy by perpetuation of self-reactivity in distinct subsets.
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| Overall design |
Chimeras were produced by transferring bone marrow from 564Igi and AicdaCreERT2-EYFP reporters (autoimmune) and AicdaCreERT2-EYFP and WT (immunized) into irradiate WT hosts. The latter were immunized with NP-OVA in alum, and boosted with NP-OVA. Fate-mapped AID-EYFP cells were isolated from spleens by Fluorescence-activated cell sorting (FACS) and analyzed using scRNAseq.
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| Contributor(s) |
Castrillon C, Carroll M |
| Citation(s) |
37341394 |
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| Submission date |
May 16, 2022 |
| Last update date |
Jun 25, 2023 |
| Contact name |
Carlos Castrillon |
| E-mail(s) |
castrilloncarlos@gmail.com
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| Organization name |
Harvard Medical School / Boston Childrens Hospital
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| Street address |
200 Longwood Ave, Warren Alpert Building
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA839019 |
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