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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.