% B Cells

B cells, a type of lymphocyte, are critical for the adaptive immune system and are primarily responsible for humoral immunity in humans.

Originating in the bone marrow, B cells produce antibodies that recognize and neutralize antigens, present antigens to T cells, and contribute to immune memory. They express specific CD markers at different stages of their development, such as CD10, CD19, CD20, and CD27. 

B cell dysfunction can lead to autoimmune diseases and cancers, and targeted therapies like Rituximab show promise in treating these conditions. 

Evaluating B cell % through assays is crucial for diagnosing and managing related disorders, ensuring effective immune response and overall health.

What are B Cells?

Description of B Cells

B cells are an important component of the immune system; specifically, they are a type of lymphocyte, or white blood cell, that are essential in the adaptive immune system.  

Lymphocytes are a type of white blood cell that circulates in the lymph and in the bloodstream.  There are two main types of lymphocytes: B cells and T cells.   

After birth, B cells originate in the bone marrow. 

The primary function of B cells is to produce antibodies, which are proteins that recognize and help neutralize or destroy specific foreign substances called antigens. 

B cells also act as antigen-presenting cells, contribute to immune memory, and help regulate other immune responses. 

B cell disruption is linked to autoimmune diseases due to loss of B-cell tolerance and inappropriate autoantibody production. B-cell abnormalities can induce autoimmunity in T-cells, suggesting B-cell depletion as a therapeutic strategy. [2.] 

Rituximab, a CD20-targeted monoclonal antibody, shows promise in treating autoimmune and neurological disorders by improving symptoms in conditions like rheumatoid arthritis and systemic lupus erythematosus. [2.] 

Normal Functions of B Cells

B cells play several crucial roles in the immune system:

Antibody Production [12.] 

The primary function of B cells is to produce antibodies. When activated, B cells differentiate into plasma cells that secrete large quantities of antibodies specific to particular antigens.

Antigen Presentation [2., 12.] 

B cells can act as antigen-presenting cells, processing and presenting antigens to T cells, which helps initiate and regulate T cell responses.

Cytokine Production [2., 12.]

B cells produce cytokines that guide lymphoid tissue development, promote effector and memory T cell responses, and negatively regulate immune responses. Additionally, B cells regulate T cell responses and inflammatory responses by producing cytokines such as IL-6, interferon-γ, tumor necrosis factor, IL-10, and IL-35. [21.]

Immune Regulation [2., 12.] 

Some B cells, particularly those producing IL-10 and IL-35, can negatively regulate immune responses, helping to maintain immune homeostasis. [21.] 

Memory Formation in the Immune System [2., 12.] 

B cells can differentiate into memory B cells, which allow for rapid and enhanced responses to subsequent antigen exposures.

Lymphoid Tissue Development [21.] 

B cells contribute to the development and organization of lymphoid tissues through the production of cytokines like lymphotoxin. 

Immune System Development and Maintenance [12.] 

B cells play a role in the normal development of the immune system, including influencing thymocyte numbers and diversity, and maintaining certain macrophage populations.

Tissue Regeneration [21.] 

Following tissue damage, B cells can produce cytokines that influence tissue regeneration in non-immunological organs following damage.

Modulation of Other Immune Cells [12.] 

B cells can influence the function of other immune cells like T cells, dendritic cells, and macrophages through cytokine production and cell-cell interactions.

Innate-like Responses [2.] 

Some B cell subsets can mount rapid, low-affinity antibody responses to typical bacterial antigens without T cell help.

These diverse functions highlight the importance of B cells not only in antibody-mediated immunity but also in broader aspects of immune regulation and tissue homeostasis.

What are the Different Types of B Cells?

B cells play diverse roles in the immune system, with three key types being antigen-presenting B cells, memory B cells, and plasma cells. 

Antigen-Presenting Cells

Antigen-presenting B cells are crucial for initiating adaptive immune responses by processing and presenting antigens to T cells. 

They express MHC class II molecules on their surface, internalize antigens via their B cell receptor (BCR), and present peptide fragments to CD4+ T cells, thereby facilitating T cell activation. 

MHC class II molecules are specialized proteins found on the surface of antigen-presenting cells that bind and present peptide fragments derived from extracellular antigens to CD4+ T helper cells, playing a crucial role in initiating adaptive immune responses. [9.] 

MHC class II molecules are essential for a healthy immune system as they initiate adaptive immune responses against pathogens. This process is crucial for effective defense against infections, particularly bacterial threats, and plays a key role in regulating overall immune function.  They are also important in having an expected vaccine response.  [9.] 

Memory B Cells

Memory B cells are responsible for long-term immunity against specific antigens. 

These cells persist for years after initial antigen exposure, respond rapidly upon re-encounter with the same antigen, and express high-affinity BCRs due to somatic hypermutation. 

This enables quick and robust secondary immune responses, providing lasting protection against previously encountered pathogens. 

Plasma Cells

Plasma cells are terminally differentiated, non-dividing cells that continuously secrete large quantities of antibodies, estimated at >5000 molecules per second. [22.] They have an expanded endoplasmic reticulum to support their primary function of antibody production. 

Plasma cells have lost most surface-bound immunoglobulins and MHC class II molecules. They are the primary source of long-term antibody production. [22.]

Plasma cells can be short-lived, lasting only days to weeks, or long-lived, persisting for months to years. 

Long-lived plasma cells are generally found in the bone marrow, which is the primary site for long-term antibody production after the resolution of an infection. They are considered crucial for maintaining serum antibody levels without needing repeated antigen exposure. [22.] 

During an immune response, plasma cells migrate to the bone marrow, where they are sustained by a stable microenvironment rich in growth factors and cytokines. This migration helps maintain long-term antibody levels. [22.] 

A goal of vaccines is to promote the production of long-lived, stable plasma cells in the bone marrow for long-term immunity. 

Diseases Associated with B Cells

Several immune-mediated diseases, including autoimmune diseases, certain cancers and certain infections, are associated with alterations in B cell function.  

Systemic Lupus Erythematosus (SLE) [17.] 

Systemic lupus erythematosus (SLE) is characterized by B cell hyperactivity leading to autoantibody production against nuclear and cytoplasmic components, such as anti-double-stranded DNA (anti-dsDNA) and anti-Smith (Sm) antibodies. 

These autoantibodies form immune complexes that contribute to tissue damage and inflammation. 

B cells in SLE also play a role in presenting antigens to T cells and secreting pro-inflammatory cytokines, further driving the disease. 

Elevated levels of B cell-activating factor (BAFF) promote B cell survival and proliferation, making BAFF inhibitors like belimumab effective in treatment. 

Overall, B cell dysfunction in SLE involves autoantibody production, antigen presentation, and cytokine secretion, necessitating targeted B cell therapies for effective management.

Rheumatoid Arthritis (RA) [24.] 

In rheumatoid arthritis (RA), B cells contribute significantly to joint inflammation, synovial tissue proliferation, and cartilage destruction through autoantibody production, cytokine secretion, and antigen presentation. 

B cells in synovial tissues function like tertiary lymphoid tissues, producing autoantibodies such as anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF), which form immune complexes that activate the complement system, exacerbating inflammation and bone erosion. 

Additionally, B cells secrete pro-inflammatory cytokines like TNF-α, IL-6, and IFN-γ, and present autoantigens to T cells, driving further immune responses. 

Specific B cell subsets, like class-switched memory B cells, are associated with disease activity and bone erosion in RA.

Multiple Sclerosis (MS) [5.] 

Multiple sclerosis (MS) is marked by inflammation and demyelination in the central nervous system, with B cells playing a critical role through antigen presentation, cytokine secretion, and antibody production. 

B cells present antigens to T cells, promoting their activation and differentiation into pro-inflammatory subsets. 

They also secrete cytokines like IL-6, which promotes the differentiation of Th17 cells, contributing to MS pathology. 

The presence of oligoclonal bands in the cerebrospinal fluid indicates ongoing B cell activity and antibody production within the CNS, contributing to demyelination and neuronal damage.

Primary Sjögren's Syndrome (pSS) [16.] 

Primary Sjögren's syndrome (pSS) involves the infiltration of B cells into exocrine glands, causing glandular dysfunction. 

B cells in pSS produce autoantibodies such as anti-Ro/SSA and anti-La/SSB, which are associated with systemic disease manifestations. They also form ectopic germinal centers in the salivary glands, supporting B cell maturation and autoantibody production. 

Elevated levels of BAFF in pSS promote B cell survival and proliferation, correlating with disease activity. 

The impaired regulatory function of B cells in pSS, along with their interactions with T follicular helper cells, sustains the autoimmune response.

X-Linked Agammaglobulinemia (XLA) [11.] 

X-Linked Agammaglobulinemia (XLA) is a primary immunodeficiency caused by mutations in the Bruton's tyrosine kinase (Btk) gene, leading to a failure in B cell development and an absence of mature B cells. 

This results in significantly low levels of all immunoglobulin isotypes, making affected individuals susceptible to recurrent infections after maternal antibodies wane. 

Diagnosis involves measuring serum immunoglobulin levels and genetic testing for Btk mutations. 

Lifelong immunoglobulin replacement therapy is essential for managing the disease.

Common Variable Immunodeficiency (CVID) [1.] and Severe Combined Immunodeficiency (SCID) [20.]

Common Variable Immunodeficiency (CVID) is characterized by low or normal B-cell counts with a significant reduction in memory B cells, leading to increased susceptibility to infections like chronic diarrhea and pneumonia. 

Patients often exhibit low expression of CD40 on B cells and ICOS on T cells, which are crucial for B cell function. 

The heterogeneity in B-cell and T-cell defects among CVID patients suggests varying underlying mechanisms. Evaluating B-cell subsets, especially memory B cells, is important for understanding and managing CVID.

Severe combined immunodeficiency (SCID) is a primary immunodeficiency disorder characterized by low to absent T cells and variable levels of B and natural killer (NK) cells. 

Infants with SCID typically develop severe infections within the first few months of life. 

Diagnosis involves detecting lymphopenia, a very low number of T cells, and impaired lymphocyte responses to mitogens. Treatment requires a protected environment and hematopoietic stem cell transplantation.

Selective IgA Deficiency [18.] 

Selective IgA deficiency is the most common primary immunodeficiency, marked by undetectable serum IgA levels while maintaining normal levels of other immunoglobulins. 

Patients often experience recurrent respiratory and gastrointestinal infections and have a higher prevalence of autoimmune diseases. 

The deficiency is due to a failure in B cells undergoing class switching to produce IgA. 

Diagnosis involves confirming low serum IgA levels and excluding other causes of hypogammaglobulinemia. Management focuses on infection control and monitoring for autoimmune complications.

B-Cell Lymphomas and Leukemias [7.] 

B-cell lymphomas are a group of cancers arising from the clonal proliferation of B-lymphocytes, often linked to genetic, environmental, and infectious factors. 

Major lymphoma subtypes include diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, mantle cell lymphoma, Burkitt lymphoma, and marginal zone lymphomas. 

Major B cell leukemias include CLL, ALL, and HCL.  Chronic Lymphocytic Leukemia (CLL), the most common type of leukemia in Western countries, predominantly affecting elderly individuals. [4.] 

Adult Acute Lymphoblastic Leukemia (ALL) is characterized by the rapid proliferation of immature lymphoid cells in the bone marrow; adult patients generally have a poorer prognosis compared to pediatric cases. [6.] 

Hairy Cell Leukemia (HCL) is a rare type of chronic leukemia that affects B lymphocytes and is characterized by the presence of abnormal B-cells with distinctive hair-like projections. [3.] 

Diagnosis involves tissue biopsy and immunohistochemical staining, while treatment varies based on the subtype and stage, typically involving chemotherapy, radiotherapy, and immunotherapy. 

Prognosis depends on the lymphoma type and stage, with aggressive forms requiring intensive treatment.

Waldenström's macroglobulinemia (WM) [10.]

Waldenström's macroglobulinemia (WM) is a rare, indolent B-cell lymphoproliferative disorder characterized by the overproduction of monoclonal immunoglobulin M (IgM) by malignant lymphoplasmacytic cells. 

Primary Immune Thrombocytopenia (ITP) [25.] 

In primary immune thrombocytopenia (ITP), B cells produce autoantibodies that target platelets, leading to decreased platelet counts and increased bleeding risk. 

Abnormalities in B-cell subsets within the bone marrow, such as reduced total B cells, naive B cells, and regulatory B cells, contribute to the disease. 

Increased long-lived plasma cells in autoantibody-positive patients suggest ongoing autoantibody production. 

Dysfunctional regulatory B cells and overactivation of the CXCL13-CXCR5 axis and BAFF/APRIL system further exacerbate the autoimmune response, providing potential targets for therapeutic intervention.

ANCA-Associated Vasculitis [8.] 

B cells are pivotal in ANCA-associated vasculitis by producing antibodies against myeloperoxidase (MPO) and proteinase 3 (PR3), leading to severe necrotizing inflammation. 

ANCA binding to neutrophils activates them, releasing factors that activate the alternative complement pathway, creating an inflammatory loop. 

Genetic predispositions and microbial mimics of ANCA antigens likely trigger the autoimmune response. 

Impaired regulation of ANCA-producing B cells by T regulatory and B regulatory cells, along with neutrophil-derived B cell-activating factors like BAFF and APRIL, perpetuate the disease.

Chronic Stress [15.]

Stress leads to elevated cortisol levels, resulting in a decrease in CD19+ B lymphocytes. This reduction is linked to a flattening of the cortisol awakening response, suggesting that chronic stress and its physiological effects can significantly impair B cell function and immune response.

Laboratory Testing for B Cell %

Test Information, Sample Collection, and Preparation

An initial assessment of B cells can be done in a complete blood count, or CBC, which is considered standard blood work. In a CBC, the total number of leukocytes, or white blood cells, is provided, along with a breakdown of different types of leukocytes.  

If the total number of lymphocytes in a CBC is low, a total B lymphocyte assay may be ordered to assess the % and type of B lymphocytes present; when used as an initial screening test, this is often ordered along with a T lymphocyte assay.  

A total B lymphocyte assay tests for levels of CD19+ and CD20+ B lymphocytes. 

This test requires a blood draw.  It is important to tell the ordering provider if you are using certain medications or supplements, which may alter the test results.   

Some specialty labs offer extensive testing for immune health and function, such as a comprehensive lymphocyte assessment: click here to learn more.

B Cell %: Normal Range and Interpretation

Optimal Levels for B Cell %

Optimal B cell counts may be interpreted according to B cell count, or B cell %.

The following levels for B cell % are offered by one lab:

Total B Cell % 6.0-18.0% [19.]

Clinical Significance of High B Cell %

A high B cell % may signal the presence of lymphoproliferative disorders, such as B-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia. 

In these malignancies, the uncontrolled proliferation of B cells can lead to various clinical manifestations including lymphadenopathy, organomegaly, and systemic symptoms. [3., 4., 6., 7.] 

Evaluating B cell % along with other biomarkers and clinical findings aids in the diagnosis, staging, and monitoring of these conditions.

Clinical Significance of Low B Cell %

A low B cell % can be observed in various conditions including:

‍

• Primary immunodeficiency disorders: some text
  • X-linked agammaglobulinemia [11.]
  • Common variable immunodeficiency (CVID) [1.]
  • Severe combined immunodeficiency (SCID) [20.] 

• Chemotherapy, radiotherapy, or suppressive immune treatments [13., 14., 23.] 

• Certain medications such as Rituximab [13.] 

• Chronic Stress [15.]

In these scenarios, the reduced % of B cells compromises the body's ability to mount an effective immune response, leaving individuals susceptible to recurrent infections and other complications. 

Monitoring B cell % can aid in the diagnosis and management of these conditions, guiding treatment decisions and assessing the effectiveness of interventions aimed at restoring normal B cell levels.

Related Biomarkers

CD19 and CD20 Expression on B Cells

CD19 and CD20 are surface markers commonly used to identify and enumerate B cells in laboratory tests such as flow cytometry and immunohistochemistry. 

Cytokine Levels and their Association with B Cell Count

Cytokines such as interleukin-6 (IL-6), interferon-gamma (IFN-γ), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-α) regulate B cell function and proliferation. [21.]

FAQ: Understanding % B Cells Biomarker

B cells are a crucial component of the immune system, playing a vital role in producing antibodies that help fight infections. Understanding the percentage of B cells in the blood can provide valuable insights into immune system health and functionality. 

What are B Cells?

B cells are a type of white blood cell that are part of the adaptive immune system. They are responsible for producing antibodies that neutralize pathogens such as bacteria and viruses, aiding in the body's defense against infections.

What is the Function of B Cells?

The primary function of B cells is to produce antibodies, which are proteins that specifically target and neutralize foreign invaders like bacteria and viruses. 

B cells also play a role in presenting antigens to T cells and maintaining immune memory, which helps the body respond more effectively to subsequent infections.

What is the % B Cells Test?

The % B Cells test refers to the percentage of B cells in relation to the total number of lymphocytes (a type of white blood cell) in the blood. 

This measurement provides insights into the balance and proportion of B cells within the immune system.

How is the % B Cells Test Measured?

The % B Cells test is typically measured using flow cytometry, a laboratory technique that analyzes the physical and chemical characteristics of cells in a blood sample. 

This method allows for accurate quantification of B cells as a percentage of total lymphocytes.

Why is it Important to Measure % B Cells?

Measuring the % B Cells can provide important information about immune system health. An abnormal percentage of B cells can indicate various conditions such as immune deficiencies, autoimmune disorders, or hematological malignancies. 

Monitoring this biomarker can help in diagnosing and managing these conditions.

What is the Difference Between B Cells and T Cells?

B cells and T cells are both types of lymphocytes, but they have different functions. 

B cells are primarily responsible for producing antibodies, while T cells have various roles including directly killing infected cells (cytotoxic T cells), helping activate other immune cells (helper T cells), and regulating immune responses (regulatory T cells).

What Does a High % B Cells Test Indicate?

A high % B Cells test can indicate conditions such as autoimmune diseases, or certain types of cancers like lymphomas. It suggests an increased production or prolonged survival of B cells in the body.

What Does a Low % B Cells Test Indicate?

A low % B Cells can suggest a weakened immune system, which may be due to factors such as chronic stress, chemotherapy, or immunodeficiency disorders. This can make the body more vulnerable to infections.

How Can % B Cells Results Vary Over Time?

The % B Cells results can fluctuate due to various factors including infections, stress, medications, and underlying health conditions. Regular monitoring may be necessary to understand trends and changes over time.

How Can I Maintain a Healthy Balance of B Cells?

Maintaining a healthy balance of B cells involves general immune health practices such as:

• Eating a balanced diet rich in vitamins and minerals

• Regular physical activity

• Managing stress effectively

• Avoiding infections and practicing good hygiene

• Following medical advice for any underlying health conditions

When Should I Consult a Doctor About my % B Cells?

You should consult a doctor if your % B Cells test is significantly outside the normal range or if you experience symptoms like frequent infections, fatigue, or unexplained weight changes. A healthcare provider can help determine the cause and appropriate treatment.

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