In situ profiling of plasma cell clonality with image-based single-cell transcriptomics.
Evan Yang1,2, Jose Aceves-Salvador1,2, Carlos Castrillon1
1Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
Biorxiv : the Preprint Server for Biology
|June 4, 2025
Summary
New BCR-MERFISH technology identifies plasma cell clones by V-gene usage. This method reveals microbiota-driven changes in mouse gut plasma cells, enhancing our understanding of adaptive immunity.
Area of Science:
- Immunology
- Molecular Biology
- Genomics
Background:
- Single-cell transcriptomics identifies cell types but misses functional variation in adaptive immunity due to unique immune receptors.
- V(D)J recombination creates diverse B-cell receptors within the same cell type, a key aspect not captured by current methods.
Purpose of the Study:
- To introduce a novel method, B-cell-receptor multiplexed error robust fluorescence in situ hybridization (BCR-MERFISH), for distinguishing plasma cell clones.
- To analyze plasma cell diversity and distribution in response to microbiota in the mouse gut.
Main Methods:
- Developed BCR-MERFISH to combine V-gene usage with transcriptome profiling for plasma cell identification.
- Validated BCR-MERFISH in cell culture and in mice with varying plasma cell diversity.
- Applied BCR-MERFISH to study mouse gut plasma cells and their response to microbiota.
Main Results:
- BCR-MERFISH accurately identifies V-gene usage in various settings.
- Revealed microbiota-dependent alterations in plasma cell abundance and clonal diversity in the mouse gut.
- Demonstrated non-uniform spatial distribution of plasma cell clones along the mouse ileum.
Conclusions:
- BCR-MERFISH provides a powerful tool to dissect plasma cell heterogeneity and function.
- The study highlights the impact of microbiota on adaptive immunity and plasma cell dynamics.
- BCR-MERFISH is anticipated to offer new insights into diverse immunological questions by integrating tissue context.
