sodium-dodecyl-sulfate and Agammaglobulinemia

We have established lymphoblastoid cell lines (LCL) from the peripheral blood of three individuals with X-linked agammaglobulinemia as well as three of their immunodeficient first-degree relatives. Lines could be induced with Epstein-Barr virus only when T lymphocytes were depleted from total mononuclear leukocytes. The LCLs derived from XLA patients expressed characteristics of IgM-secreting plasmacytes, including intense cytoplasmic fluorescence after staining with anti-mu, easily detectable amounts of IgM in culture supernatants, and radiolabeled IgM with both heavy and light chains in culture media and cell lysates. The cell lines induced from blood of the first-degree relatives of these patients were more varied. They often exhibited multiple isotypes for both heavy and light chains in different cells or expressed a B-lymphocyte phenotype (easily detectable surface Ig but no Ig secretion). These studies suggest that B-cell precursors are present in peripheral blood of individuals with classical XLA . Differentiation of such cells to mature cells of the B lineage can be accomplished using Epstein-Barr virus after removal of T cells.

Topics: Adult; Agammaglobulinemia; Cell Line; Cell Transformation, Viral; Cells, Cultured; Female; Fluorescent Antibody Technique; Herpesvirus 4, Human; Humans; Immunoglobulin M; Immunoglobulins; Lymphocyte Depletion; Male; Sodium Dodecyl Sulfate; T-Lymphocytes; X Chromosome

Peripheral blood lymphocytes of two patients with infantile X-linked agammaglobulinemia could neither synthesize nor secrete immunoglobulins in detectable amounts. Peripheral blood lymphocytes of patients with common variable type of hypogammaglobulinemia synthesize but do not secrete immunoglobulins. Serologic precipitation with antiimmunoglobulin serum and acrylamide-gel analysis of immunoglobulins synthesized by lymphocytes of these patients showed predominant mu-chain, as compared to immunoglobulins synthesized by normal lymphocytes. Biosynthesis and secretion of immunoglobulins by cultured lymphoblast cells from normal persons was very much analogous to that of lymphocytes of hypogammaglobulinemic patients. These findings suggest that lymphocytes of patients with common variable type of hypogammaglobulinemia are immature B cells like cultured lymphoblast cells, and that a block in cytodifferentiation of IgM to IgG-producing cells is present in their B cells.

Topics: Adult; Agammaglobulinemia; Animals; Carbohydrates; Carbon Radioisotopes; Cell Fractionation; Cells, Cultured; Electrophoresis, Polyacrylamide Gel; Female; Galactose; Glucosamine; Hemocyanins; Humans; Immune Sera; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Leucine; Lymphocytes; Male; Middle Aged; Rabbits; Sodium Dodecyl Sulfate; Tritium