Analysis of VH and VL genes of a monospecific human anti-myosin antibody produced by a B cell from the primary repertoire
| Autor: | J, Laroche-Traineau, M, Biard-Piechaczyk, M J, Jacobin, J L, Chagnaud, B, Pau, A, Nurden, G, Clofent-Sanchez |
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| Rok vydání: | 2000 |
| Předmět: |
B-Lymphocytes
Herpesvirus 4 Human Hybridomas Base Sequence Genes Immunoglobulin Molecular Sequence Data Immunoglobulin Variable Region Antibodies Monoclonal Sequence Homology Sequence Analysis DNA Myosins Cell Transformation Viral Antibody Specificity Humans Immunoglobulin Light Chains Amino Acid Sequence Cloning Molecular Fluorescent Antibody Technique Indirect Immunoglobulin Heavy Chains Autoantibodies Thrombasthenia |
| Zdroj: | Human antibodies. 9(3) |
| ISSN: | 1093-2607 |
| Popis: | Epstein-Barr virus (EBV) transformation of B lymphocytes from a Glanzmann's thrombasthenia patient with a serum antibody to the integrin alpha IIb beta 3, led to the immortalization of a B cell secreting a monospecific IgM monochonal antibody (MAb), B7, reactive with platelet myosin. Analysis of B7 V genes revealed minimally mutated sequences: the immortalized B cell issued from the primary repertoire, with no evidence of an in vivo selection by myosin. The V genes were here compared with sequences of human MAbs available on databases to more clearly understand the monospecificity of the B7 MAb. B7 V genes were closely identical to rearranged V genes in clones with self-specificities, often secreting polyreactive antibodies. In contrast, B7 is an unmutated monoreactive human MAb able to recognize myosin with a high avidity. Comparison of the CDR3H sequence with that of MAbs in databases supports a central role for the CDR3H subdomain in determining monospecificity. Our results suggest the existence of a monospecific autoreactive B cell compartment, besides the well-known polyspecific one, susceptible to be the template of pathogenic autoreactivity, characterized by antibodies of high affinity and specificity. |
| Databáze: | OpenAIRE |
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