Rat salivary gland reveals a more restricted IgA repertoire than ileum. 2008

Maaike Stoel, and Willem N H Evenhuis, and Frans G M Kroese, and Nicolaas A Bos
Department of Cell Biology, Immunology Section, University Medical Center Groningen, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.

Secretory IgA is the most abundantly produced Ig in different mucosal tissues, such as the gastrointestinal tract and the salivary glands. These mucosal tissues are considered to be part of the common mucosal immune system. The specificity and immunoglobulin (Ig) VH gene repertoire of the IgA producing cells of both tissues is still largely unknown. To investigate the diversity of the antibody repertoire of IgA producing cells at different mucosal effector sites, we analysed used Ig VH genes by H-CDR3 spectrotyping and VH gene sequencing of both ileum and salivary gland IgA producing cells of PVG rats. Both types of tissues showed a limited diversity for the two major VH gene families, J558 and PC7183. The salivary gland showed even less diversity than the ileum of the same rat. Cloning and sequencing of used IgA VH genes confirmed the very restricted usage of VH genes since multiple sets of clonally related sequences in both types of tissues were found. More clones were found in salivary gland than in ileum and both tissues did not have shared VDJ joining regions. IgA derived from salivary gland used germline or near germline VH genes, whereas the ileal VH genes contained more mutations. Furthermore, clonal evolution patterns from all analyzed VH gene sequences of the salivary gland IgA producing cells show mainly randomly acquired somatic mutations, in contrast to the clonal evolution patterns often observed as a consequence of affinity maturation in germinal center reactions in peripheral lymphoid organs and Peyer's patches. Our results imply that IgA producing cells in the salivary gland are neither induced at the same place nor selected in the same way as the IgA producing cells in the ileum. The function of the IgA secreted by salivary gland is very likely a first line of defense with (near) germline encoded IgA, whereas in the intestine the majority of utilized IgA VH genes show evidence of somatic hypermutation.

UI MeSH Term Description Entries
D007070 Immunoglobulin A Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions. IgA,IgA Antibody,IgA1,IgA2,Antibody, IgA
D007082 Ileum The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.
D007135 Immunoglobulin Variable Region That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions. Variable Region, Ig,Variable Region, Immunoglobulin,Framework Region, Immunoglobulin,Fv Antibody Fragments,Fv Fragments,Ig Framework Region,Ig Variable Region,Immunoglobulin Framework Region,Immunoglobulin Fv Fragments,Immunoglobulin V,Antibody Fragment, Fv,Antibody Fragments, Fv,Fragment, Fv,Fragment, Fv Antibody,Fragment, Immunoglobulin Fv,Fragments, Fv,Fragments, Fv Antibody,Fragments, Immunoglobulin Fv,Framework Region, Ig,Framework Regions, Ig,Framework Regions, Immunoglobulin,Fv Antibody Fragment,Fv Fragment,Fv Fragment, Immunoglobulin,Fv Fragments, Immunoglobulin,Ig Framework Regions,Ig Variable Regions,Immunoglobulin Framework Regions,Immunoglobulin Fv Fragment,Immunoglobulin Variable Regions,Regions, Immunoglobulin Variable,Variable Regions, Ig,Variable Regions, Immunoglobulin
D007143 Immunoglobulin Heavy Chains The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa. Immunoglobulins, Heavy-Chain,Heavy-Chain Immunoglobulins,Ig Heavy Chains,Immunoglobulin Heavy Chain,Immunoglobulin Heavy Chain Subgroup VH-I,Immunoglobulin Heavy Chain Subgroup VH-III,Heavy Chain Immunoglobulins,Heavy Chain, Immunoglobulin,Heavy Chains, Ig,Heavy Chains, Immunoglobulin,Immunoglobulin Heavy Chain Subgroup VH I,Immunoglobulin Heavy Chain Subgroup VH III,Immunoglobulins, Heavy Chain
D009928 Organ Specificity Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen. Tissue Specificity,Organ Specificities,Specificities, Organ,Specificities, Tissue,Specificity, Organ,Specificity, Tissue,Tissue Specificities
D010581 Peyer's Patches Lymphoid tissue on the mucosa of the small intestine. Patches, Peyer's,Peyer Patches,Peyers Patches
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000917 Antibody Formation The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS. Antibody Production,Antibody Response,Antibody Responses,Formation, Antibody,Production, Antibody,Response, Antibody,Responses, Antibody
D000921 Antibody-Producing Cells Cells of the lymphoid series that can react with antigen to produce specific cell products called antibodies. Various cell subpopulations, often B-lymphocytes, can be defined, based on the different classes of immunoglobulins that they synthesize. Antibody-Producing Cell,Antibody-Secreting Cell,Antibody-Secreting Cells,Immunoglobulin-Producing Cells,Immunoglobulin-Secreting Cells,Antibody Producing Cell,Antibody Producing Cells,Antibody Secreting Cell,Antibody Secreting Cells,Cell, Antibody-Producing,Cell, Antibody-Secreting,Cell, Immunoglobulin-Producing,Cell, Immunoglobulin-Secreting,Cells, Antibody-Producing,Cells, Antibody-Secreting,Cells, Immunoglobulin-Producing,Cells, Immunoglobulin-Secreting,Immunoglobulin Producing Cells,Immunoglobulin Secreting Cells,Immunoglobulin-Producing Cell,Immunoglobulin-Secreting Cell
D012469 Salivary Glands Glands that secrete SALIVA in the MOUTH. There are three pairs of salivary glands (PAROTID GLAND; SUBLINGUAL GLAND; SUBMANDIBULAR GLAND). Gland, Salivary,Glands, Salivary,Salivary Gland

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