hematology and oncology
Overview of Plasma Cell Disorders
Pathophysiology
(For structural features and classification of the immunoglobulins, see Antibodies .) After developing in the bone marrow, undifferentiated B cells enter peripheral lymphoid tissues, such as the lymph nodes, spleen, and gut (eg, Peyer patches). Here, they begin to differentiate into mature cells, each of which can respond to a limited number of antigens. After encountering the appropriate antigen, some B cells undergo clonal proliferation into plasma cells. Each clonal plasma cell line is committed to synthesizing one specific immunoglobulin antibody that consists of 2 identical heavy chains (gamma [γ], mu [μ], alpha [α], delta [δ], or epsilon [ε]) and 2 identical light chains (kappa [κ] or lambda [λ]). A slight excess of light chains is normally produced, and urinary excretion of small amounts of free polyclonal light chains (≤40 mg/24 hours) is normal. In plasma cell disorders, disproportionate proliferation of one clone in the bone marrow results in a corresponding increase in the serum level of its product, the monoclonal immunoglobulin protein (M-protein). M-proteins may consist of both heavy and light chains or of only one type of chain. Complications of plasma cell proliferation and M-protein production include the following: Damage to organs (particularly the kidneys due to Hypercalcemia or toxic light chains secreted by the malignant plasma cells): Some M-proteins show antibody activity against self-antigens. Impaired immunity: There is decreased production of other immunoglobulins and impaired T-cell responses. Bleeding tendency: M-protein may cause bleeding by coating platelets, inactivating clotting factors, increasing blood viscosity, and other mechanisms. Amyloidosis : M-protein can form fibrillar deposits within organs, most commonly the heart and kidneys. Osteoporosis , Plasma cell disorders can vary from asymptomatic, stable conditions (in which only the monoclonal protein is present) to progressive cancers (eg, Multiple Myeloma —for classification, see table 