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The Differentiation of Vertebrate Immune Cells

The Differentiation of Vertebrate Immune Cells. In the immune system, two types of cells participate directly in defense against pathogens.

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The Differentiation of Vertebrate Immune Cells

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  1. The Differentiation of Vertebrate Immune Cells • In the immune system, two types of cells participate directly in defense against pathogens. • Plasma B cells produce and secrete immunoglobulins (antibodies), and killer T cell produce membrane-bound proteins that act as receptors for various substances. • B cell antibodies and T cell receptors bind to specific antigens. A cell must make many varieties of these proteins because there are many potential pathogens.

  2. An Antigen-Antibody Complex

  3. Structure of an Antibody Molecule

  4. Human Antibody Genes • Two light chain loci: the  on chromosome 2 and  on chromosome 22 • One heavy chain locus on chromosome 14. • Each locus consists of a long array of gene segments.

  5. Gene Segments for a Kappa Polypeptide • An LV gene segment, encoding a leader peptide, which is removed later, and the N-terminal 95 amino acids of the variable region of the kappa light chain. (76 gene segments in humans; 40 of these are functional) • A J gene segment, encoding the last 13 amino acids of the variable region of the kappa light chain. (5 gene segments in humans) • A C gene segment, encoding the constant region of the kappa light chain. (1 gene segment in humans)

  6. The Kappa Locus • During B cell development, the kappa light chain gene that will be expressed is assembled from one LV segment, one J segment, and the C segment by somatic recombination. • Segment joining is mediated by recombination signal sequences adjacent to each gene segment by a protein complex including RAG1 and RAG2 (recombination activating gene proteins 1 and 2).

  7. Many Different Antibodies Can Be Produced • 40 LV segments  5 J segments  1 C segment = 200 kappa light chains. • Recombination of gene segments can create 120 lambda light chains and 6600 different heavy chains. • Combinatorial assembly of these allows production of 2,112,000 different antibodies. • Even more antibodies are possible due to variation in recombination sites and hypermutability of the variable regions.

  8. Evidence for DNA Rearrangement During Immune Cell Differentiation

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