Simultaneous presence, in one serum, of four monoclonal antibodies that might correspond to different steps in a clonal evolution from polyreactive to monoreactive antibodies.
Three monoclonal IgG of different subclasses (IgG1, IgG2, and IgG4) and one IgA1 were isolated from the serum of patient Per suffering from an immunocytic sarcoma. All four monoclonal Ig shared the same N-terminal sequence of their H chains (VH3). Furthermore, their kappa-chains exhibited identical isoelectric charges and N-terminal sequences (VK2) and expressed the same private idiotope. A strong antitubulin activity was found in IgA1Per and in two of the three monoclonal IgGPer. The specificity was restricted to tubulin for IgA1Per and IgG4Per, whereas IgG1Per also displayed significant polyreactive bindings and IgG2Per failed to react with any of the Ag tested. The monoreactive IgG4Per, as well as the polyreactive IgG1Per, bound a large peptide in the central part of both alpha and beta subunits of tubulin (amino acid position 100 to 300). In contrast, the monoreactive IgA1Per bound to a rarely detected epitope close to residue 310 of these subunits. The tubulin epitope recognized by polyreactive IgG1Per was similar to that of germ-line-encoded polyreactive antibodies. It is hypothesized that IgG4Per- and IgA1Per-producing cells derive from the IgG1Per polyreactive clone after somatic events leading to the production of monoreactive antibodies.
Houdayer
M
M
Unité d'Immunohématologie et d'Immunopathologie, Institut Pasteur, Paris, France.
Bouvet
J P
JP
Wolff
A
A
Magnac
C
C
Guillemot
J C
JC
Borche
L
L
Dighiero
G
G
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood* / Q000737:chemistry; D000916:Antibody Diversity; D000939:Epitopes / Q000097:blood / Q000737:chemistry; D006801:Humans; D007106:Immune Sera / Q000032:analysis*; D007070:Immunoglobulin A / Q000097:blood* / Q000737:chemistry; D007074:Immunoglobulin G / Q000097:blood* / Q000737:chemistry; D007143:Immunoglobulin Heavy Chains / Q000097:blood / Q000737:chemistry; D007145:Immunoglobulin kappa-Chains / Q000097:blood / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007106:Immune Sera; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains