All Igs consists of 2 heavy chains and 2 light chains. The heavy chains define the Ig class as Ig A (alfa), IgG (gamma) IgM (my), IgD (delta) and IgE (epsilon). The light chains are designated kappa and lambda. Whatever type of heavy chain each Ig-molecule consists of either 2 kappa or 2 lambda light chains. Igs are produced in mature B-lymphocytes from from the virgin small B-lymphocyte through its activated stages until the plasma cell stage, but the amount of Ig in different B-lymphocytes vary considerably. Virgin unstimulated B-lymphocytes contain only small amounts of cytoplasmic my-chains. During maturation B-lymfocytes in the mantle zone express surface IgM and IgD. When B-cells are activated and transform into plasma cells, they become capable of cytoplasmic accumulation and secretion of Igs, while the membranous expression is lost. Most activated B-cells produce IgM but about 10% accumulate and secrete another Ig-type, mostly IgG or IgA. Ig-molecules containing kappa light chains are slightly more frequent than molecules containing lambda.
While benign (reactive) B-lymphocytic populations produce Ig-molecules containing an almost equal amount of kappa and lambda light chains, i.e. the number of cells producing kappa is more or less equal to the number producing lambda, neoplastic B-lymphocytic populations has light chain restriction (i.e., are monoclonal) producing either kappa or lambda. Consequently, demonstration of light chains is the most important procedure in the diagnosis of neoplasms of B-lymphocytes (lymphomas and leukemias). The amount of Ig produced in individual types of B-lymphocytic neoplasia vary and is often small, demanding a sensitive technique for detection. About 80% of non-Hodgkin lymphomas are B-cell lymphomas, of which the large majority express surface (s) IgM, although the expression in small cell lymphoma/chronic lymphocytic leukaemia is weak. Plasmacytoma/multiple myeloma do not show sIgM. Lymphoplasmacytic lymphoma most often shows sIgM, while plasmacytoma/multiple myeloma show sIgG in 50% and sIgA in 20%.
Light chain restriction is the single most important marker for neoplasms of B-lymphocytic origin. Demonstration of heavy chains be sometime be of aid in the study of malignant lymphomas, as lymphoplasmacytic lymphomas are usually focally IgM positive, while plasmacytoma/multiple myeloma in most cases express strong cytoplasmic IgG or IgA. Precursor B-cell neoplasms are are Ig negative.
IgM: Tonsil is recommendable as control for the demonstration of membranous IgM. Virtually all mantle zone B-cells of the germinal centres must show a moderate to strong, distinct and predominantly membranous staining reaction, while plasma cells and immunoblasts must show a strong cytoplasmic staining reaction. T-cells must be negative and no or only a weak general background staining must be seen. IgK: Tonsil is an appropriate control: Approximately half of the peripheral mantle zone B-cells must show a distinct membranous staining reaction for IgK, while the remaining mantle zone B-cells (which are IgL producing) should be unstained. IgL: Normal tonsil is appropriate control tissue: approximately 50% of the mantle zone B-cells should show a distinct membrane staining reaction, while the rest should be unstained.
Selected references
Jaffe ES et al (Eds) WHO Classification Tumours of Haematopoietic and Lymphoid Tissue. IARC Press 2001. Ashton-Key M, Jessup E, Isaacson PG. Immunoglobulin light chain staining in paraffin-embedded tissue using a heat mediated epitope retrieval method. Histopathology. 1996 Dec;29(6):525-31.
26.11.13 - PJ/MV/LE