All About B Cells: Antibodies and Beyond

July 11, 2025

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Written by Joanna Wirkus, PhD

Introduction

B cell basics

B cell differentiation

Antibodies

Monoclonal antibodies in medicine

Cytokine production

Antigen presentation

B cells and gene therapy: animal and human research

B lymphocytes were first described in the 1960s by scientists Cooper and Good, who discovered the site of B cell maturation in birds by halting antibody production after irradiating the Bursa of Fabricius in chicks. Much has been discovered about B cells in the past 60 years, but they remain incompletely understood because sampling them from the bone marrow and spleen is difficult.

In this blog, we’ll explore how B cells develop and their renowned antibody-producing abilities. We’ll also cover B cell cytokine production, antigen presentation, and current developments in human B cell gene editing research for next-generation treatments.

B Cell Differentiation

The bone marrow is the primary B-lymphoid organ and serves as the vital microenvironment for B cell maturation. The complex differentiation journey begins with a multipotent CD34+ hematopoietic stem cell that commits to the lymphoid lineage and eventually develops into a naïve mature B cell. See Figure 1 for a diagram of B cell development.

Figure 1, the developement process of a B cell. from HSC to B cell — Figure 1

On the B cell’s surface, the B cell receptor (BCR) is essential for binding to antigens and jumpstarting the production and secretion of antibodies. During the bone marrow maturation process, B cells can generate many versions of the heavy and light chain immunoglobulin BCR by splicing their own genes through the Variable, Diversity, Joining (VDJ) gene recombination system. This system creates remarkable diversity in specificity to recognize and defend against a wide range of disease-causing pathogens.

Through this differentiation process, the B cells are tested for their recognition of self -versus-non-self, with additional receptor editing or induction of apoptosis for B cells that are primed to attack host tissues. When this self-tolerance testing process malfunctions, autoimmune conditions like lupus can develop.

The mature naïve B cell exits the bone marrow and enters the peripheral circulation, where it can migrate to secondary lymphoid organs, such as the spleen. In the spleen, B cells become activated and more specialized as a result of direct interactions with antigens or by antigens presented by follicular dendritic cells or T cells. This antigen stimulation by T cells leads to differentiation into memory B cells or plasma cells.

Plasma cells are short-lived and secrete high levels of antibodies. In contrast, memory cells are long-lived and promote long-term immunity. When memory cells encounter the same antigen they are primed to recognize, they proliferate and differentiate into specialized, antibody-producing plasma cells.

Antibodies – B Cell Immunology Basics: Features & Functions

Unlike the vigilant, nonspecific, and fast-acting innate immune system that recognizes common pathogen markers, the longer-acting adaptive immune system is trained to mount an attack against specific disease-causing microbes by recognizing, binding to, and neutralizing the invaders.

The humoral immune response is the body’s adaptation to eliminating infectious organisms by producing antibodies designed to target specific bacteria, viruses, and fungi that manage to evade the first-line defenses of the innate immune system. Antibodies, also known as immunoglobulins, fight active infections and prevent reinfections. B cells are the only cells that synthesize and secrete antibodies, and a fully differentiated plasma cell can produce thousands of these antigen-binding proteins every second. Furthermore, the average adult has billions of B cells circulating in the blood and lymph, with each B cell producing a single type of antibody.

The antibody is a Y-shaped protein with an amino acid sequence designed for high affinity and specificity to a particular epitope on a foreign microbial antigen. Through opsonization, antibodies bind to and inactivate invading microbes, marking them for recognition and clearance by macrophages via receptor-mediated phagocytosis.

Recent advances in biotechnology have enabled researchers to leverage in silico research methods to better understand the antibody-producing potential of B cells. Published in Nature, researchers at The Scripps Research Institute in La Jolla, CA shared their findings using computational methods to analyze B cell transcripts from peripheral blood mononuclear cells (PBMCs) collected via leukapheresis, estimating that the human body can produce a repertoire of one quintillion (one million trillion) unique antibodies.

To discover and engineer improved antibodies, biochemistry professor Dr. Peter Kim at Stanford University is using a general protein language model trained on proteins and their amino acid sequences—a form of generative artificial intelligence (AI). Their findings have been published in Nature Biotechnology and Science.

The Power of Antibodies as New Treatments: Monoclonal Antibodies

Monoclonal antibodies (mAbs) advanced the biologics-based medical paradigm by harnessing the immune system’s power to produce effective antibodies at scale. In 1986, the FDA approved the first mAb medicine, Orthoclone, designed to treat acute rejection of renal transplants.

Generating a hybridoma, the first step in creating mAbs, begins with the fusion of a single antibody-producing B cell with a murine myeloma cell line—an immortalized, non-antibody-producing cancerous B cell (e.g., NS0 or SP2/0). Combining the antibody-producing properties of the B cell with the immortality of the cancer cell results in a hybrid cell capable of indefinitely replicating the identical antibody.

Three decades later, mAbs have become versatile biologics, with over 150 FDA-approved mAbs to treat more than 100 diseases, spanning applications from cancer and autoimmune diseases to rare disorders.

Blockbuster immunotherapeutic mAbs such as Yervoy®, Opdivo®, and Keytruda® generated a combined $41 billion in revenue in 2023 and have led to complete, durable remission of melanoma in some individuals.

Beyond leveraging biomimicry to modernize medical treatments, mAbs are utilized in laboratories across the globe daily for immunohistochemistry, flow cytometry, Western blotting, and ELISA. By allowing scientists to characterize cells, proteins, and pathways, mAbs have been fundamental improving our understanding of the mechanisms of action of drugs and nutrients.

Beyond Antibodies: B Cell Cytokine Production 

In 1984, scientists began to uncover the B cell’s vital role in regulating the adaptive and innate immune response by secreting various cytokines depending on their state of differentiation and microenvironment.  

Some of the key proinflammatory chemical messengers produced by effector B cells include: 

Tumor Necrosis Factor Alpha (TNF-α)

Recruits macrophages and CD4+ T cells to the site of infection and promotes the expansion of Th1 and Th2 cells.

Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) 

In response to elevated levels of lipopolysaccharides, such as in sepsis, toll-like receptors are activated in Innate Response Activator B cells to amplify the innate immune response. Myeloid cells become activated, proliferate, and differentiate, increasing the number of neutrophils and macrophages.

Interleukin-6 (IL-6)   

Promotes the immune response by supporting the differentiation of naive T cells into Th17 / Th1 cells. This cytokine also has anti-inflammatory effects by promoting regulatory B cells to produce IL-10, described below.

For homeostatic downregulation of the immune response, regulatory B cells produce anti-inflammatory cytokines such as:  

IL-10 

Inhibits pro-inflammatory cytokine production, macrophage activation and proliferation, and proinflammatory T cells while stimulating immunoregulatory T cells. Promotes B cell survival, differentiation, and antibody production.

Research on B cell produced cytokines has led to a better understanding of autoimmune disease. For example, an article in Cell Press Immunity reported that IL-10 producing B cells were found to be enriched in peripheral blood in healthy subjects, while this cytokine producing ability was impaired in individuals with systemic lupus erythematosus.

Antigen presentation

B cell antigen presentation is an important crosslink between the humoral and cytotoxic arms of the adaptive immune response. T lymphocytes are activated by antigens presented by antigen presenting cells (APC), such as macrophages, dendritic cells, and B cells. B cells can recognize specific antigens at very low concentrations through the B cell receptor (BCR). Once the BCR binds to the antigen, it is internalized through endocytosis and is presented on the cell surface MHC II complex to a CD4+ helper T cell. This initiates T cell activation, proliferation, and differentiation, and stimulates B cell proliferation and differentiation into plasma and memory B cells.

Cell and Gene Therapy Basic Research in B cells

Research from the James lab in the Center of Immunotherapy and Immunity at Seattle Children’s Research Institute published in Nature Communications found that genetically engineered B cells could engraft and remain functional for over a year in animal models. Researchers isolated B cells from healthy donor peripheral blood mononuclear cells (PBMCs) and used an adeno-associated viral vector to gene edit the B cells using CRISPR. The genetically engineered B cells were infused into immunodeficient mice, along with the key human IL-6 cytokine, and they maintained their genetic and metabolic functionality long term. The researchers predict this B cell-based technology could be used to deliver drugs once replacing continuous redosing.

Beyond Basic Research: B Cell Gene Therapy in Patients

Immusoft in Seattle is currently investigating an autologous B cell therapy for Hurler Syndrome in Phase 1 clinical trials.

Our understanding of B cell biology is increasing daily and the long-term therapeutic and research applications are immeasurable.

To support the advancement of this developing field, CGT Global offers B cells customized to meet the needs of any research project.

For 15 years, CGT Global has supported scientists worldwide conducting cutting-edge research in cell and gene therapy by providing the highest-quality human primary cells.

CGT Global delivers B cells isolated from umbilical cord blood and Leukopaks from peripheral blood. All cells are procured using IRB-approved consent forms, in a CLIA-certified and FDA-registered laboratory.

Our B cells are isolated from mononuclear cell populations (which are ~5-10% B cells) using positive or negative immunomagnetic separation techniques and characterized with flow-cytometry.

CGT Global B Cells

CD19+ B Cells (Cord Blood) • Source: Cord Blood • Separation Method: Positive or Negative Selection • Vial Size: 1 million cells/vial

CD19+ B Cells (Peripheral Blood) • Source: Peripheral Blood • Separation Method: Negative Selection • Custom Option: Positive Selection Available • Vial Size: 10 million cells/vial (bulk or custom available)

CD19+ CD27– Naïve B Cells • Source: Peripheral Blood • Separation Method: Negative Selection • Vial Sizes: 0.5, 1, or 2 million cells/vial

CD19+ CD27+ Memory B Cells • Source: Peripheral Blood • Separation Method: Negative Selection and Enrichment • Vial Sizes: 0.5, 1, or 2 million cells/vial

Cryopreserved B cells with viability ≥ 80% and purity ≥ 90%

The CGT Difference: Your cells, your way!

We offer a variety of options to customize your order:

Large recallable donor pool with customizable donor characteristics – including vaccination and allergy status
Custom cell types available (including plasma cells). Ask our team!
Fresh or cryopreserved cells
Custom selection methods (positive or negative selection)
Flexible shipping options including same-day, overnight, and international shipments with specialty courier services