Also Known As
Immunoglobulin Gene Rearrangement
B-cell Gene Clonality Molecular Genetic Tests
BCGR
Formal Name
B-cell Gene Rearrangement
This article was last reviewed on
This article waslast modified on 2 May 2023.
At a Glance
Why Get Tested?

To help diagnose a B-cell lymphoma; to detect and evaluate residual cancer cells

When To Get Tested?

When a doctor thinks that you may have a B-cell lymphoma; sometimes to evaluate the effectiveness of treatment or to evaluate for recurrent disease

Sample Required?

A bone marrow or other tissue biopsy procedure is performed by a doctor or other trained specialist. Body fluid samples are obtained by inserting a needle into the body cavity and withdrawing a portion of the fluid with a syringe. Sometimes, a blood sample is obtained by inserting a needle into a vein in the arm.

Test Preparation Needed?

None

On average it takes 7 working days for the blood test results to come back from the hospital, depending on the exact tests requested. Some specialist test results may take longer, if samples have to be sent to a reference (specialist) laboratory. The X-ray & scan results may take longer. If you are registered to use the online services of your local practice, you may be able to access your results online. Your GP practice will be able to provide specific details.

If the doctor wants to see you about the result(s), you will be offered an appointment. If you are concerned about your test results, you will need to arrange an appointment with your doctor so that all relevant information including age, ethnicity, health history, signs and symptoms, laboratory and other procedures (radiology, endoscopy, etc.), can be considered.

Lab Tests Online-UK is an educational website designed to provide patients and carers with information on laboratory tests used in medical care. We are not a laboratory and are unable to comment on an individual's health and treatment.

Reference ranges are dependent on many factors, including patient age, sex, sample population, and test method, and numeric test results can have different meanings in different laboratories.

For these reasons, you will not find reference ranges for the majority of tests described on this web site. The lab report containing your test results should include the relevant reference range for your test(s). Please consult your doctor or the laboratory that performed the test(s) to obtain the reference range if you do not have the lab report.

For more information on reference ranges, please read Reference Ranges and What They Mean.

What is being tested?

This test detects characteristic changes (rearrangements) in specific genes in B-cells. This information can be helpful in diagnosing a B-cell lymphoma.

B-cells are a type of lymphocyte (a kind of white blood cell, WBC) that produces antibodies in response to infections or other "foreign invaders." Rearrangements in certain parts of their DNA called immunoglobulin genes are a normal part of their development. These rearrangements are associated with the development of a large repertoire of diverse B-cells, allowing them to protect against many different kinds of infections. The final order in which the genes are rearranged is called a gene rearrangement profile. Within any normal population (sample) of B-cells, the cells and their gene rearrangement profiles are very diverse.

In a lymphoma, the B-cells in affected tissue (such as blood, bone marrow or lymph node) are identical and their gene rearrangement profiles are likewise identical. Lymphomas arise when an abnormal B-cell begins to produce numerous identical copies of itself (clones). The cloned cells grow and divide uncontrollably, crowding out normal cells.

A B-cell immunoglobulin gene rearrangement test evaluates the B-cells in a person's sample to determine whether the majority of B-cell rearrangement profiles are diverse or identical. This information, along with clinical signs and symptoms and results of other laboratory tests, can help clarify a person's diagnosis, or evaluate the persistence of low level disease or recurrence of lymphoma.

The majority of non-Hodgkin lymphomas are B-cell lymphomas.

For additional details about B-cells and this testing, see Common Questions below.

Accordion Title
Common Questions
  • How is it used?

    B-cell immunoglobulin gene rearrangement tests are used to help diagnose non-Hodgkin B-cell lymphomas and evaluate for residual or recurrent disease after treatment.

    Lymphomas arise when an abnormal B-cell begins to produce numerous identical copies of itself (clones). The cloned cells grow and divide uncontrollably, crowding out normal cells. There are many different types of B-cell lymphoma and each has different characteristics, prognoses, and a likely response to therapy. Several classification systems have been used to describe them. The most recent is the World Health Organization's (for more on this, see the Lymphoma article).

    Testing for B-cell lymphomas involves several types of tests:

    • Full Blood Count (FBC) and a WBC differential to evaluate the number, types, and maturity of white blood cells present in the blood. Results may reveal an increased number of lymphocytes and/or presence of abnormal lymphocytes.
    • Evaluation of blood smear, bone marrow, lymph node and/or other tissue biopsy samples. These samples are examined under a microscope, usually by a Haematopathologist or a Histopathologist.
    • In all cases, immunophenotyping is performed on blood, bone marrow, or other tissue (e.g. enlarged lymph node, tumour) using a method such as flow cytometry or immunohistochemistry. This test detects the presence or absence of certain markers on the membrane of the cells or inside the cells. These commonly used markers are called clusters of differentiation (CD) and are listed numerically. Patterns of antigens (presence or absence) can provide information as to whether the B-cells are clones (monoclonal) and can further help classify a B-cell lymphoma.

    A proliferation of B-cells can be benign or malignant. If, at this point, there is still no conclusion whether a person has a benign or malignant lymphocyte population, B-cell immunoglobulin gene rearrangement testing can be performed to help clarify the diagnosis.

    Testing may sometimes be performed to evaluate the effectiveness of lymphoma treatment, that is, to detect residual (low level disease that cannot be seen under a microscope) or recurrent disease (the continued presence of abnormal monoclonal B-cells).

  • When is it requested?

    Testing is performed when a person has signs and symptoms that suggest a lymphoma, such as:

    • One or more swollen but painless lymph nodes—depending on the site of the affected lymph node, symptoms may involve areas of the chest, armpit, neck, abdomen, or groin area, for example
    • Fatigue
    • Fever
    • Night sweats
    • Unexplained weight loss
    • Neurologic symptoms that may suggest central nervous system involvement

    Findings from a FBC and differential may be the first indication that a person might have a blood cell cancer as symptoms of early lymphoma may be absent, mild, or nonspecific.

    Testing may be done when other laboratory tests indicate that a lymphoma may be present and/or when other tests are inconclusive. Some examples include:

    •  An increased number of lymphocytes, especially abnormal-looking lymphocytes, as determined with a FBC and a blood smear examination
    • Signs of lymphoma in a tissue biopsy, body fluid or bone marrow sample
    • With immunophenotyping (e.g. flow cytometry, immunohistochemistry), antigen groupings that are inconclusive for a B-cell lymphoma, or when the doctor wants to confirm a diagnosis of lymphoma based on histopathology and immunophenotyping

    Testing may also be requested when a person has been treated for a lymphoma to evaluate the effectiveness of treatment, that is, to detect residual or recurrent disease.

  • What does the test result mean?

    Results of testing are typically interpreted by a doctor who specialises in dealing with blood, blood cells, and bone marrow cells (a Haematologist). Results must be interpreted in conjunction with clinical findings, other test results including immunophenotyping information, an understanding of the strengths and limitations of different testing methods, and with an understanding of the range of findings in a "normal" lymphocyte cell population.

    In general, if a significant clonal B-cell population is detected and other associated tests are in agreement, then it is likely that the individual tested has a B-cell lymphoma.

    Examples of lymphomas that may be detected by gene rearrangement testing include:

    • B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma
    • Burkitt lymphoma
    • Diffuse large B-cell lymphoma
    • Follicular lymphoma
    • Hairy cell leukemia
    • Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia
    • Mantle cell lymphoma
    • Marginal zone B-cell lymphoma
  • Is there anything else I should know?

    Sample collection and testing may need to be repeated when the initial sample does not contain enough DNA to test.

    The detection of a clonal immunoglobulin gene rearrangement is not synonymous with the presence of B-cell lymphoma. An individual may have a clonal B-cell population and not have cancer. Conditions such as autoimmune disorders, immune suppression, and immune deficiencies are sometimes associated with small clonal B-cell populations. This means that one or more groups of cloned B-cells may be present in a person's lymphocyte population without it being considered a lymphoma.

    If a person is negative for a clonal B-cell immunoglobulin gene rearrangement, the person may still have lymphoma. A test may also be negative if the test method is not sensitive enough to detect the rearrangement, or if the clonal lymphocytes from the person tested have mutations that are not detected by the test.

    Since false positive and false negative results can be associated with this testing, the results must be interpreted in the context of other clinical and pathologic findings.

    Since plasma cells are terminally differentiated B-cells, immunoglobulin gene rearrangement testing can also be seen in plasma cell neoplasms, such as multiple myeloma and plasmacytoma.

  • Should everyone with a B-cell lymphoma have B-cell gene rearrangement testing?

    No. This testing is only required if routine diagnostic procedures are not sufficient to make an accurate diagnosis.

  • Can results of testing be used to determine the course of my cancer?

    No. A positive testing result only helps to confirm a diagnosis of B-cell lymphoma and does not point to a specific subtype of B-cell lymphoma. The clinical course and response to treatment are generally determined by the subtype of a person's lymphoma, along with certain genetic abnormalities and clinical staging of the disease.

  • How common are B-cell gene rearrangements?

    B-cell immunoglobulin genes are constantly rearranging themselves to produce unique immunoglobulins. These rearrangements are normal.

  • What are some other details about B cells?

    B-cells contain specific areas (genes) in their DNA that code for the production of antibodies (also known as immunoglobulins).The immunoglobulin genes consist of numerous, discontinuous coding segments. As B-cells develop and mature, these DNA segments are rearranged in a controlled fashion such that each mature B-cell has a unique rearrangement profile. When the body is exposed to antigen, such as bacteria or viruses, the B-cell immunoglobulin genes undergo a permanent rearrangement in order to produce antibodies directed against that threat. For instance, if a person is exposed to a rubella virus, then some of the B-cells change and become rubella antibody-secreting cells. If a person is exposed to a hepatitis B virus, then some of the B-cells become hepatitis B antibody-secreting cells.

    The body maintains a library of antibody "blueprints" so that the next time it is exposed to a threat, it can use the B-cell blueprint to rapidly produce large quantities of a specific antibody. This means that the population of mature B-cells is normally diverse (polyclonal) with small amounts of many different kinds of antibodies and temporary increases in specific antibodies as needed to counter an exposure. In this setting, B-cell expansions are polyclonal, with each clone containing relatively few cells and no one clone predominating.

    With a B-cell lymphoma, an abnormal B-cell is formed and begins to clone itself. The identical, cloned (monoclonal) cells do not function normally, their replication is not controlled by the immune system, and they may not die as normal cells do. A cancerous monoclonal population of B-cells accumulates, begins to crowd out normal cells, and may eventually spread through the lymphatic system and blood to other lymph nodes or tissue, including bone marrow.

    All of the monoclonal B-cells produced will have an identical immunoglobulin gene rearrangement profile. The neoplastic clones are generally large, and therefore the clonal cells are the predominant B-cells present in involved tissue (e.g., lymph node, bone marrow, blood, body fluid). Detection of a predominant immunoglobulin gene rearrangement profile often indicates the presence of a neoplastic B-cell population. This can help establish the diagnosis of a B-cell lymphoma or evaluate for residual or recurrent disease after treatment.