B Cell Count

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 count 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 Count

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 number 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 Count: Normal Range and Interpretation

Optimal Levels for B Cell Count

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

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

Total B Cell Count 90-400 cells/uL [19.]

Clinical Significance of High B Cell Count

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

Clinical Significance of Low B Cell Count

A low B cell count 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 number 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 count 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.]

Frequently Asked Questions (FAQs) on B Cell Count

The FAQ section addresses common questions and concerns about B Cell Count, providing clear and concise answers for better understanding.

What is a B Cell Count?

A B Cell Count measures the number of B cells in a blood sample. B cells are a type of white blood cell that plays a crucial role in the immune system by producing antibodies to fight infections.

What is the Normal Range for a B Cell Count?

The normal range for B Cell Count can vary depending on the laboratory and the population being tested. 

Generally, a normal B Cell Count ranges from 100 to 400 cells per microliter of blood. 

It's important to consult with your healthcare provider to understand your specific results.

What Does a High B Cell Count Mean?

A high B Cell Count can indicate several conditions including chronic infections, autoimmune disorders, or certain types of cancers such as leukemia or lymphoma. 

It’s essential to follow up with your healthcare provider for further evaluation and diagnosis.

What Causes a High B Cell Count?

Several factors can cause a high B Cell Count, including:

• Lymphoproliferative disorders (e.g., leukemia, lymphoma)

• Some chronic infections

• Some autoimmune diseases

What is the Significance of a B Cell Count in Lymphoproliferative Disorders?

B cell count aids in the evaluation of lymphoproliferative disorders such as B-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia. 

In these conditions, an abnormally high B cell count is often observed, reflecting the uncontrolled proliferation of malignant B cells. Monitoring B cell count can aid in disease staging, prognostic assessment, and evaluating treatment response and relapse.

How is A B Cell Count Used in Monitoring Treatment Response and Relapse?

In patients undergoing treatment for lymphoproliferative disorders, B cell count serves as a valuable marker for monitoring treatment response and detecting potential relapse. 

A decrease in B cell count following treatment can indicate a positive response, while a persistent or increasing count may signal treatment resistance or disease progression.

How is the B Cell Count Useful in Guiding Treatment Decisions?

The assessment of B cell count, in conjunction with other clinical and laboratory findings, can guide treatment decisions for patients with lymphoproliferative disorders and immunodeficiencies. 

For instance, in certain B-cell malignancies, such as DLBCL, B cell count may influence the choice of therapy, including the consideration of targeted therapies like CAR T-cell therapy or hematopoietic cell transplantation.

What Does a Low B Cell Count Mean?

A low B Cell Count may suggest a weakened immune system, which could be due to various factors such as viral infections, chemotherapy, or diseases like HIV/AIDS. A low count can make the body more susceptible to infections.

What Causes a Low B Cell Count?

A low B Cell Count can be caused by:

• Chemotherapy or radiation therapy

• Bone marrow disorders

• Immune deficiencies

• Chronic stress

How is a B Cell Count Test Performed?

A B Cell Count test is typically performed through a blood sample. The sample is analyzed in a laboratory using techniques such as flow cytometry to count the number of B cells.

Can B Cell Count Results Vary Over Time?

Yes, B Cell Count results can vary due to several factors, including infections, stress, medications, and underlying health conditions. Regular monitoring may be necessary for individuals with fluctuating counts.

How Can I Improve My B Cell Count?

Improving your B Cell Count depends on the underlying cause. General recommendations include:

• Maintaining a healthy diet

• Getting regular exercise

• Managing stress

• Practicing good hygiene measures such as regular hand washing to avoid infections

• Following medical advice for any underlying conditions

When Should I See a Doctor About My B Cell Count?

You should see a doctor if your B Cell Count is significantly outside the normal range, or if you experience symptoms such as frequent infections, fatigue, or unexplained weight loss. 

A healthcare provider can help determine the cause and appropriate treatment.

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