Cell-extrinsic Microenvironment based Protein-Secreting Plasma Cell Differentiation Service

Brief Description

The program of B cell transition into protein production plasma cell is influenced by molecules secreted from surrounding various cells, such as cytokines derived from activated T cells, cellular receptors, and chemokines. These extracellular signals can modify the gene expression landscape and are crucial to deciding cell destiny. Moreover, they are important for plasma cell migration and maintenance in the bone marrow, which is principal for performing a long-lasting function of cells. Based on years of research on plasma cell development mechanisms, Creative Biolabs offers protein-secreting plasma cell generation service by coordinating genome editing and supplementing extracellular signals to facilitate B cell transition toward a plasma cell.

Extracellular Microenvironment Mediated Plasma Cell Generation Service at Creative Biolabs

After site-specific modification of B cells for exogenous protein production and secretion, the engineered cells could be differentiated into long-lived plasma cells resident in bone marrow using in vitro and in vivo lineage switch methods. Creative Biolabs' superior expertise can help facilitate your plasma cell differentiation discovery and development studies and provides services covering the entire process of generation and assessment.

Specific Differentiation Methods

  • Differentiation in Mouse Models

As the antibody-secreting cell matures in vivo with T cell help, the engineered B cell can differentiate to protein-secreting cells after transfer into NSG mouse. The differentiation process has two steps.

Step 1

The first step is the extrafollicular response. Lymphoid Follicular B cell is activated, transited to B lymphoblasts, and differentiated to short-lived plasmablasts.

Step 2

Activated B cells form a germinal center (GC) with the effect of Tfh cells, producing memory B cells and long-lived plasma cells with enhanced affinity and improved antibody secretion.
  • Differentiation Ex Vivo
    • Many conditions and factors involved in generating high-affinity antibody-secreting plasma cells in vivo have been effectively substituted ex vivo, using the same molecules with stimuli on Tfh cell as signal molecular.
    • As CD40L, IL-4, IL-5, and IL-21 can be used to recapitulate Tfh cell-derived signal, and LPS and unmethylated CpG DNA can be used to recapitulate T cell-independent stimuli.

Characteristics of the Two Differentiation Approaches

  • The defined ex vivo stimulation system can guide engineered B cells to differentiate into plasma cells with high reproducibility assured on both molecular and cellular levels.
  • The ex vivo differentiation method has the advantage of delivering non-antibody proteins in certain dosages and the rare possibility of DNA sequence mutation in the target protein.
  • Both can induce B-cell transition to bone marrow-resident plasma cells sustained for a long term.

Differentiated Plasma Cell Analysis Service

The differentiation process and composition of the mixed cell cultures can be evaluated using multiple advanced and accurate methods.

1 Phenotypes Identification
  • Morphology
  • Cell marker identification using flow cytometry
  • Active protein secretion
2 Genetics
  • Single-cell transcriptomics analysis
  • Genomic DNA analysis
4 In Vivo Behavior
  • Transfer to mouse models
  • Monitor homing to and retaining in the BM

Creative Biolabs is devoted to engineering B cells to secret a high capacity of proteins and transit to long-lived plasma cells located in the bone marrow. We are committed to developing the most effective way to guide your engineered B cell differentiation. If you are interested in our service, please contact us and consult our experts.

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