Single Cell BCR Sequencing
Single cell BCR sequencing is a high-throughput technology that enables the analysis of B cell receptor (BCR) sequences and expression profiles at single-cell resolution. BCRs are membrane-bound immunoglobulins expressed on the surface of B cells that specifically recognize foreign antigens, initiating the humoral immune response. Upon antigen exposure, B cells are activated through BCR recognition and subsequently undergo clonal expansion, somatic hypermutation, and class switching to produce high-affinity antibodies. Traditional BCR sequencing is typically performed on bulk cell populations, yielding averaged signals across many cells and thus failing to resolve the clonal architecture or functional states of individual B cells. In contrast, single cell BCR sequencing allows the pairing of immunoglobulin heavy chain (IGH) and light chain (IGK or IGL) sequences with corresponding transcriptome data from the same cell, enabling the simultaneous characterization of immune diversity, B cell lineage trajectories, functional states, and immunological features under disease conditions. This technology facilitates the tracking of individual immune responses, the identification of key clonal expansions following infection or vaccination, and high-resolution studies in areas such as tumor immune surveillance, autoimmune disease research, and therapeutic antibody development. As a result, single cell BCR sequencing has become a powerful tool for dissecting B cell-mediated immune mechanisms and offers new avenues for personalized medicine. Furthermore, it can be integrated with other single-cell multi-omics approaches—such as single cell TCR sequencing, transcriptomics, and spatial omics—to construct a more comprehensive map of the immune system. This multidimensional strategy is particularly valuable in complex tissues such as tumors and peripheral blood mononuclear cells (PBMCs), where it enables a deeper understanding of the immune microenvironment from multiple perspectives and provides rich datasets to elucidate immune regulatory networks.
The core of single cell BCR sequencing lies in linking the BCR repertoire with the gene expression profile of individual cells. This is typically achieved through single-cell isolation using microfluidic platforms, droplet-based encapsulation systems, or microwell-based sorting. Once isolated, mRNA from each cell is reverse-transcribed and tagged with a unique cell-specific barcode, enabling the BCR sequence and transcriptome data to be precisely matched at the single-cell level. The barcoded libraries are then subjected to high-throughput sequencing, followed by computational reconstruction and analysis to retrieve critical parameters including paired IGH and IGK/IGL sequences, somatic mutations in the variable regions, clonal lineage relationships, antibody isotypes, and cellular states.
Implementing single cell BCR sequencing involves several technical challenges. First, due to extensive V(D)J recombination and somatic hypermutation, BCR sequences exhibit high diversity, making the accurate pairing of heavy and light chains a critical analytical challenge. Second, B cells comprise diverse subtypes—such as naïve B cells, memory B cells, and plasma cells—each with distinct transcriptional signatures and BCR repertoires. Thus, accurate identification and classification of B cell subsets require integration with transcriptomic data. Third, in polyclonal samples, BCR expression levels can vary widely, and low-abundance clones may be underrepresented or missed altogether, necessitating high sequencing sensitivity and robust noise reduction algorithms. Despite these challenges, single cell BCR sequencing offers distinct advantages over traditional methods. It not only enables precise mapping of BCR sequence architecture at the single-cell level but also provides insights into the activation states, differentiation trajectories, and functional potential of individual B cells through clonal lineage tracking.
MtoZ Biolabs specializes in the advanced integration of single cell omics and proteomics technologies and is dedicated to delivering high-quality analytical services to our clients. Partner with MtoZ Biolabs to uncover the cellular codes underlying the immune system.
MtoZ Biolabs, an integrated chromatography and mass spectrometry (MS) services provider.
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