Analysis of VH and VL genes of a monospecific human anti-myosin antibody produced by a B cell from the primary repertoire.
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.
Laroche-Traineau
J
J
CNRS UMR 5533, Hôpital Cardiologique, Pessac, France.
Biard-Piechaczyk
M
M
Jacobin
M J
MJ
Chagnaud
J L
JL
Pau
B
B
Nurden
A
A
Clofent-Sanchez
G
G
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000918:Antibody Specificity; D001323:Autoantibodies / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D001483:Base Sequence; D002472:Cell Transformation, Viral; D003001:Cloning, Molecular; D019084:Fluorescent Antibody Technique, Indirect; D005803:Genes, Immunoglobulin / Q000235:genetics*; D004854:Herpesvirus 4, Human; D006801:Humans; D006825:Hybridomas; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000235:genetics* / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008969:Molecular Sequence Data; D009218:Myosins / Q000276:immunology*; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D013915:Thrombasthenia / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D009218:Myosins