Switch Recombination in Normal IgA1+B Lymphocytes

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 4; pp. 1323 - 1327
• Main Authors: Irsch, Johanns, Irlenbusch, Sigrid, Radl, Jiri, Burrows, Peter D., Cooper, Max D., Radbruch, Andreas H.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15-02-1994; National Acad Sciences; National Academy of Sciences
• Subjects: Antibodies; Antigens, CD - analysis; B lymphocytes; B-Lymphocyte Subsets - immunology; Biological and medical sciences; Blood; Blood Cells - immunology; Cell Cycle; Cell lines; Cell Separation - methods; Cellular biology; Cellular immunity; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genetic loci; Genotype; Humans; Immunity (Disease); Immunobiology; Immunoglobulin A - genetics; Immunoglobulin A - immunology; Immunoglobulin Class Switching; Immunoglobulin Constant Regions - genetics; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Isotypes; Immunophenotyping; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Myeloid cells; Natural killer cells; Plasma cells; Receptors, Antigen, B-Cell - genetics; Receptors, Antigen, B-Cell - immunology; Recombination, Genetic; Spleen cells; Human; Biological fluid; Cell cloning; Recombination; Typing; B-Lymphocyte; IgA1; In vitro; Cell surface
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.4.1323

Most B lymphocytes in normal individuals express two classes of cell-surface immunoglobulins, IgM and IgD. The specificity of the two antigen receptors is identical since they are produced by transcription and differential splicing of the same variable region gene segment to the heavy-chain constant region gene segments for both μ and δ heavy chains. B lymphocytes expressing other immunoglobulin isotypes, IgG, IgA, or IgE, are rare and not well characterized. Particularly controversial is the molecular mechanism of their isotype switch. Here we use high-gradient magnetic cell sorting and fluorescence-activated cell sorting to purify surface IgA1-bearing B lymphocytes from human blood for cellular and molecular analysis. These cells express no immunoglobulin class other than IgA1 and are a relatively uniform population with regard to expression of other cell-surface molecules. They are resting cells in terms of cell cycle and activation marker analysis. The molecular basis for class switching in the IgA1+cells is not differential transcription or splicing. Rather, switch recombination involving deletion of DNA has occurred on both immunoglobulin heavy-chain gene loci, including the allelically excluded one, and appears to have been directed to IgA1 under normal physiological conditions.