Affiliations: [a] CNRS UMR 5533, Hôpital Cardiologique, 33604 Pessac, France | [b] CNRS UMR 9921, Faculté de Pharmacie, 34000 Montpellier, France | [c] GISIR, Centre de Vie Condorcet, 33608 Pessac, France
Correspondence:
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Correspondence and reprints to: Dr. J. Laroche-Traineau, UMR 5533 CNRS, Hôpital Cardiologique, 33604, Pessac, France. Tel.: +33 5 56 55 68 08; Fax: +33 5 56 55 65 31.
Abstract: Epstein-Barr virus (EBV) transformation of B lymphocytes from a Glanzmann’s thrombasthenia patient with a serum antibody to the integrin αIIbβ3, led to the immortalization of a B cell secreting a monospecific IgM monoclonal 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.
Keywords: human antibody, immunoglobulin variable region, B cell repertoire, nucleotide sequence, myosin
