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Individual Cell Level Full-Length Immunoglobulin Profiling Service

Introduction Services Application Platform Advantages FAQs Resources

The Imperative for Cognate Pair Fidelity: Overcoming Conventional Limitations

Fig.1 http://47.109.42.40:8006/images/20180710235143_7334.jpg. (Creative Biolabs Authorized)

The profound specificity and diversity of the adaptive immune response are encoded within the B cell receptor (BCR) repertoire. An individual BCR, and its secreted antibody counterpart, is a heterodimeric protein composed of a heavy (IgH) and a light (Igκ or IgL) chain. The combinatorial pairing of these two chains dictates the antigen-binding specificity and, consequently, the functional capacity of the B cell. Therefore, a precise and comprehensive interrogation of the immune repertoire necessitates the recovery of this cognate pairing information from individual B cells.

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Limitations of Conventional Antibody Repertoire Profiling

While numerous approaches have been developed, each carries critical compromises that limit biological interpretability and practical throughput.

Approach Strengths Key Limitations
Bulk NGS of Ig Genes High throughput; captures global repertoire diversity. Loses the native linkage between IgH and IgL; pairing must be computationally inferred, yielding biologically meaningless associations.
Individual-Cell PCR (IcPCR) + Sanger Sequencing Preserves true IgH–IgL pairing. Extremely low throughput (hundreds of cells); labor-intensive; costly.
Linked-amplicon or Synthetic Pairing Methods (Short-read NGS) Physically couples IgH and IgL amplicons. Truncated reads; incomplete variable/constant region coverage; cannot fully reconstruct functional antibodies.

The Need for a Next-Generation Solution

To overcome these significant bottlenecks, a technology is required that simultaneously achieves three critical objectives:

Such a capability is indispensable for therapeutic antibody discovery, mechanistic studies of vaccine responses, and the deep elucidation of B cell clonal dynamics in infectious disease, autoimmunity, and oncology.

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A High-Fidelity, End-to-End Profiling Solution

Fig.2 Analyzing the data. (Creative Biolabs AI)

At Creative Biolabs, we provide a comprehensive, end-to-end solution for full-length immunoglobulin profiling with true cell-level resolution. Our advanced platform enables the simultaneous recovery of complete, paired IgH and IgL sequences from thousands of individual B cells in a individual experiment, transforming complex biological samples into a high-fidelity, functionally meaningful digital immune repertoire.

Service Workflow

Stage Key Steps & Highlights
1. Sample Preparation & Cell Isolation We accept diverse input materials — including PBMCs, splenocytes, lymph node suspensions, and bone marrow. Our team can also perform upstream tissue dissociation and high-dimensional FACS sorting to isolate specific B-cell subsets such as antigen-specific, memory, or plasma cells. This enables direct linkage of phenotype and sequence.
2. Cell-Level Barcoding & Amplification Each individual B cell is processed in a discrete microenvironment containing a unique molecular barcode. Using our proprietary two-dimensional barcoded primer matrix, full-length IgH, Igκ, and IgL transcripts are reverse-transcribed and amplified. All products from a individual cell share the same barcode, ensuring precise identity tracking.
3. Library Construction & Sequencing Barcoded amplicons from all cells are pooled into a individual NGS library and sequenced using our high-throughput, long-read platform, producing millions of high-quality, full-length reads.
4. Bioinformatic Reconstruction Our custom-built bioinformatics pipeline uses barcode information as a digital identifier to reconstruct native IgH/IgL pairs for each B cell. The resulting data are error-corrected, fully annotated, and ready for in-depth analysis.
5. Data Delivery Clients receive a comprehensive package including:
• Raw sequencing files
• High-confidence paired IgH/IgL sequences
• V(D)J gene usage and isotype classification
• Clonotype grouping by junction similarity
• Detailed somatic hypermutation (SHM) analysis and statistical summary

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Powering Therapeutic Discovery and Immunological Insight

The data generated by our Individual Cell Full-Length Immunoglobulin Profiling service provides an unprecedented resource for both basic research and therapeutic development. The potential applications are vast and transformative:

Therapeutic Antibody Discovery

This is the most direct application. By isolating antigen-specific B cells, we provide the exact, full-length paired sequences of human (or other species) monoclonal antibodies. This information enables the immediate in silico selection, gene synthesis, and in vitro expression of recombinant mAbs for functional screening (e.g., neutralization assays, affinity measurements) without the ambiguities of chain mis-pairing.

Vaccinology and Infectious Disease

Our service allows for the deep interrogation of B cell responses to vaccination or natural infection. Researchers can track the clonal evolution of antibody-secreting cells, map the acquisition of somatic hypermutations over time, and identify the specific clonal lineages responsible for generating broadly neutralizing antibodies.

Autoimmunity and Oncology

By profiling B cell repertoires in disease states, it is possible to identify the specific autoreactive or tumor-infiltrating B cell clonotypes. This information is critical for understanding disease pathogenesis, identifying novel diagnostic biomarkers, and developing targeted B cell-depleting or -modulating therapies.

B Cell Lineage Tracing

The acquisition of full-length sequence data, complete with SHM patterns, enables the high-resolution construction of B cell phylogenetic trees. This allows researchers to trace the evolutionary pathway of an antibody response from a naive precursor to a mature, high-affinity, class-switched B cell.

Systems Immunology

When combined with individual-cell transcriptomics (icRNA-seq) or other individual-cell modalities, our BCR profiling service contributes to a high-dimensional, multi-omic understanding of B cell fate. This integration links BCR specificity directly to the cell's transcriptional state, phenotype, and function.

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Technology Platform Designed for Precision and Scale

The technical foundation of our service is the proprietary Sequencing and Analysis Platform. This integrated system is engineered specifically to address the unique challenges of BCR repertoire analysis and offers distinct advantages for our clients.

Full-Length Precision

Optimized chemistry and long-read protocols ensure complete Ig coverage—from the 5′ leader through the V(D)J and into the constant region.

Accurate Mutation Detection

An advanced error-correction pipeline distinguishes true somatic hypermutations from PCR or sequencing artifacts using consensus-based algorithms and quality scoring.

Scalable Throughput

Processes thousands to tens of thousands of B cells per run, providing statistically robust insights into both rare and dominant clones.

Cross-Species Compatibility

A universal barcoding system enables individual-cell Ig amplification from diverse species, supporting broad immunology and therapeutic research applications.

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The Creative Biolabs Advantages

Fig.3 http://47.109.42.40:8006/images/20180711045246_6975.jpg. (Creative Biolabs Authorized)

Choosing Creative Biolabs for individual-cell immunoglobulin profiling provides distinct, service-oriented advantages rooted in our deep scientific expertise and technological specialization.

Fidelity of Cognate Pairing
Fidelity of Cognate Pairing
Our primary advantage is the unambiguous preservation of the native IgH and IgL chain pairing. This is non-negotiable for the functional assessment and downstream cloning of monoclonal antibodies.
Full-Length Sequence Acquisition
Full-Length Sequence Acquisition
We provide complete sequence information for both chains. This is a significant advancement over 5' RACE or short-read linkage methods, as it provides the constant region sequence (defining isotype and effector function) and ensures the entire V(D)J region is available for cloning and SHM analysis.
High-Sensitivity and Throughput
High-Sensitivity and Throughput
We transcend the "several hundred cell" limit of traditional icPCR. By analyzing thousands of cells, we provide the statistical power needed to uncover rare clones and accurately quantify the clonal diversity of the B cell compartment.
Expert Scientific Support
Expert Scientific Support
As a team of immunologists and bioinformaticians, we provide more than just data. We offer dedicated project consultation and in-depth data interpretation support to ensure the results are biologically meaningful and actionable.

From Individual Cell to Full Insight — Start Your Profiling Project Today.

FAQs

  1. Does your service capture the constant region and determine the antibody isotype?

    Yes. A key advantage of our platform is the amplification of full-length Ig transcripts. This means our sequencing data includes the constant region, allowing for the precise determination of the isotype (IgM, IgG, IgA, IgE) and subclass (e.g., IgG1, IgG2) for every paired antibody sequence.

  2. How does your analysis pipeline distinguish true somatic hypermutations (SHMs) from PCR and sequencing errors?

    This is a critical challenge that our platform is specifically designed to address. Our analytical pipeline uses a multi-layered approach. First, we employ high-fidelity DNA polymerases during the icPCR amplification step to minimize error introduction. Second, our specialized bioinformatic pipeline analyzes the quality scores and sequencing depth for each position. By building a consensus and applying statistical filters, we can computationally distinguish low-frequency, stochastic technical artifacts from high-confidence, biological SHMs, even those present in a individual cell.

  3. Can you perform this service for species other than human and mouse?

    Absolutely. Our two-dimensional barcoded primer matrix is universally compatible. Our scientific team possesses extensive experience in designing and validating species-specific primer sets for the amplification of Ig genes. We have successfully profiled repertoires from non-human primates, rabbits, camelids (for single-domain antibody discovery), and other species.

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Resources

Use the resources in our library to help you understand your options and make critical decisions for your study.

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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